Regional specificities in the distribution, chemical phenotypes, and coexistence patterns of neuropeptide containing nerve fibres in the human anal canal

Despite the pivotal clinical significance of the human anal canal, little is known about its total and specific innervation. This study assessed the comparative distribution and histotopology of nerve fibres immunoreactive for neural markers and a variety of regulatory active neuropeptides in the human anal canal by light microscopic immunohistochemistry. Depending on the epithelial zone and region of the anal canal, the neural elements were differentially immunoreactive for the pan-neural marker protein gene product 9.5, the catecholamine marker tyrosine hydroxylase, the neuroendocrine marker chromogranin A, and various neuropeptides. Protein gene product 9.5-immunoreactive nerve fibres we…

The Tachykinin Neuroimmune Connection in Inflammatory Pain

Identification of a tumor-reactive T-cell repertoire in the immune infiltrate of patients with resectable pancreatic ductal adenocarcinoma

The devastating prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDA) presents an urgent need for the development of therapeutic strategies targeting disseminated tumor cells. Until now, T-cell therapy has been scarcely pursued in PDA, due to the prevailing view that it represents a poorly immunogenic tumor.We systematically analyzed T-cell infiltrates in tumor biopsies from 127 patients with resectable PDA by means of immunohistochemistry, flow cytometry, T-cell receptor (TCR) deep-sequencing and functional analysis ofProminent T-cell infiltrates, as well as tertiary lymphoid structures harboring proliferating T-cells, were detected in the vast majority of biopsies f…

Dexamethasone desensitizes hepatocellular and colorectal tumours toward cytotoxic therapy

The glucocorticoid dexamethasone is frequently used as co-treatment in cytotoxic cancer therapy, e.g. to prevent nausea, to protect normal tissue or for other reasons. While the potent pro-apoptotic properties and the supportive effects of glucocorticoids to tumour therapy in lymphoid cells are well studied, the impact to cytotoxic treatment of colorectal and hepatocellular carcinoma is unknown. We tested apoptosis-induction, viability, tumour growth and protein expression using 8 established cell lines, 18 surgical specimen and a xenograft on nude mice. In the presence of dexamethasone we found strong inhibition of apoptosis in response to 5-FU, cisplatin, gemcitabine or gamma-irradiation,…

Individualisierte Chirurgie bei Rektumkarzinomen

Die anteriore oder tiefe anteriore Rektumresektion in Kombination mit einer partiellen (PME) oder totalen mesorektalen Exzision (TME) sind die derzeitigen Standardverfahren in der Chirurgie der Rektumkarzinome. Diese Operationen werden laparoskopisch oder in konventioneller Technik durchgefuhrt. Die wesentlichen Phasen der Operation sind: 1. Mobilisierung von Sigma und Colon descendens; 2. Durchtrennung der A. und V. mesenterica inferior; 3. Durchtrennung des Colon descendens; 4. Mobilisierung des Rektums in PME- oder TME-Technik; 5. Absetzen des Rektums; 6. Anastomosierung; 7. Anlage eines protektiven Stomas (optional). Technische Probleme und schwierige Entscheidungssituationen entstehen …

Neurotransmitter in Pankreasnerven: Ein Beitrag zur Schmerzgenese bei chronischer Pankreatitis

Ursache und Pathogenese des langjahrigen Schmerzsyndromes bei chronischer Pankreatitis sind nach wie vor ungeklart. Ein neues Konzept der Schmerzgenese bei chronischer Pankreatitis, namlich spezifische Veranderungen an den Pankreasnerven, wurde vor kurzem erstmals beschrieben (1). Es handelt sich hierbei neben einer Vermehrung und Grosenzunahme von extrinsischen und intrinsischen neuralen Strukturen im Pankreas um eine Zerstorung des perineuralen Bindegewebes, welches als wirksame Schutzbarriere gegenuber humoralen und cellularen Einflussen im gesunden menschlichen Pankreas fungiert.

Oligometastases of Gastrointestinal Cancer Origin

Peptidergic Innervation in Chronic Pancreatitis

The reason for the generation and continuation of chronic pain in chronic pancreatitis is unclear [6, 10, 11, 13, 61, 117]. Current concepts of the neurobiology of pain point to the possible role of various neuropeptides in pain processing and inflammation [8, 29, 32, 33, 44, 60, 64, 65, 68, 79, 104, 112]. A key function has been ascribed to the proinflammatory and pronociceptive peptides of the tachykininin (TK) family (8, 44, 104, 109]. That the tachykinin substance P (SP) may be involved in chronic inflammatory and painful disease of the gastrointestinal system is evidenced by a selective increase in the density of tachykinin receptors in the bowels of patients suffering from Crohn’s dis…