Joerg Lindenmann

Early enteral feeding compared with parenteral nutrition after oesophageal or oesophagogastric resection and reconstruction

After resective and reconstructive surgery in the gastrointestinal tract, oral feeding is traditionally avoided in order to minimize strain to the anastomoses and to reduce the inherent risks of the postoperatively impaired gastrointestinal motility. However, studies have given evidence that the small bowel recovers its ability to absorb nutrients almost immediately following surgery, even in the absence of peristalsis, and that early enteral feeding would preserve both the integrity of gut mucosa and its immunological function. The aim of this study was to investigate the impact of early enteral feeding on the postoperative course following oesophagectomy or oesophagogastrectomy, and reconstruction. Between May 1999 and November 2002, forty-four consecutive patients (thirty-eight males and six females; mean age 62, range 30-82) with oesophageal carcinoma (stages I-III), who had undergone radical resection and reconstruction, entered this study (early enteral feeding group; EEF). A historical group of forty-four patients (thirty-seven males and seven females; mean age 64, range 41-79; stages I-III) resected between January 1997 and March 1999 served as control (parenteral feeding group; PF). The duration of both postoperative stay in the Intensive Care Unit (ICU) and the total hospital stay, perioperative complications and the overall mortality were compared. Early enteral feeding was administered over the jejunal line of a Dobhoff tube. It started 6 h postoperatively at a rate of 10 ml/h for 6 h with stepwise increase until total enteral nutrition was achieved on day 6. In the controls oral enteral feeding was begun on day 7. If compared to the PF group, EEF patients recovered faster considering the duration of both stay in the ICU and in the hospital. There was a significant difference in the interval until the first bowel movements. No difference in overall 30 d mortality was identified. A poor nutritional status was a significant prognostic factor for an increased mortality. Early enteral feeding significantly reduces the duration of ICU treatment and total hospital stay in patients who undergo oesophagectomy or oesophagogastrectomy for oesophageal carcinoma. The mortality rate is not affected.

Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries

The potassium channel TWIK-related acid sensitive potassium (TASK)-1 channel, together with other potassium channels, controls the low resting tone of pulmonary arteries. The Src family tyrosine kinase (SrcTK) may control potassium channel function in human pulmonary artery smooth muscle cells (hPASMCs) in response to changes in oxygen tension and the clinical use of a SrcTK inhibitor has resulted in partly reversible pulmonary hypertension. This study aimed to determine the role of SrcTK in hypoxia-induced inhibition of potassium channels in hPASMCs. We show that SrcTK is co-localised with the TASK-1 channel. Inhibition of SrcTK decreases potassium current density and results in considerable depolarisation, while activation of SrcTK increases potassium current in patch-clamp recordings. Moderate hypoxia and the SrcTK inhibitor decrease the tyrosine phosphorylation state of the TASK-1 channel. Hypoxia also decreases the level of phospho-SrcTK (tyr419) and reduces the co-localisation of the TASK-1 channel and phospho-SrcTK. Corresponding to this, hypoxia reduces TASK-1 currents before but not after SrcTK inhibition and, in the isolated perfused mouse lung, SrcTK inhibitors increase pulmonary arterial pressure. We propose that the SrcTK is a crucial factor controlling potassium channels, acting as a cofactor for setting a negative resting membrane potential in hPASMCs and a low resting pulmonary vascular tone.

PCK2 activation mediates an adaptive response to glucose depletion in lung cancer

Cancer cells are reprogrammed to utilize glycolysis at high rates, which provides metabolic precursors for cell growth. Consequently, glucose levels may decrease substantially in underperfused tumor areas. Gluconeogenesis results in the generation of glucose from smaller carbon substrates such as lactate and amino acids. The key gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK), has been shown to provide metabolites for cell growth. Still, the role of gluconeogenesis in cancer is unknown. Here we show that the mitochondrial isoform of PEPCK (PCK2) is expressed and active in three lung cancer cell lines and in non-small cell lung cancer samples. PCK2 expression and activity were enhanced under low-glucose conditions. PEPCK activity was elevated threefold in lung cancer samples over normal lungs. To track the conversion of metabolites along the gluconeogenesis pathway, lung cancer cell lines were incubated with 13C3-lactate and label enrichment in the phosphoenolpyruvate (PEP) pool was measured. Under low glucose, all three carbons from 13C3-lactate appeared in the PEP pool, further supporting a conversion of lactate to pyruvate, via pyruvate carboxylase to oxaloacetate, and via PCK2 to phosphoenolpyruvate. PCK2 small interfering RNA and the pharmacological PEPCK inhibitor 3-mercaptopicolinate significantly enhanced glucose depletion-induced apoptosis in A549 and H23 cells, but not in H1299 cells. The growth of H23 multicellular spheroids was significantly reduced by 3-mercaptopicolinate. The results of this study suggest that lung cancer cells may utilize at least some steps of gluconeogenesis to overcome the detrimental metabolic situation during glucose deprivation and that in human lung cancers this pathway is activated in vivo.

Vitamin D and Cancer Mortality: Systematic Review of Prospective Epidemiological Studies

Accumulating evidence from experimental and epidemiological studies suggests that vitamin D deficiency might be a causal risk factor for cancer and therewith associated mortality. We performed a systematic review in Medline up to February 2012 to identify prospective studies on 25-hydroxyvitamin D (25[OH]D) and cancer mortality as well as on 25(OH)D and survival in cancer patients. Our search retrieved 13 studies on cancer-specific mortality and 20 studies on overall mortality in cancer patients. Data on 25(OH)D and cancer mortality were mainly derived from general populations. The results were inconsistent and yielded either no, inverse or positive associations. By contrast, the majority of studies in cancer patients showed that patients with higher 25(OH)D levels had a decreased risk of mortality. This relationship was particularly evident in cohorts of colorectal cancer patients. In contrast, there was no indication for increased mortality risk with higher vitamin D levels in any cancer cohort. In conclusion, the relationship of vitamin D status and cancerspecific mortality is still unclear and warrants further studies. Our results provide a strong rationale to perform prospective randomized controlled studies to document a potential effect of vitamin D supplementation on survival in cancer patients.

The influence of elevated levels of C-reactive protein and hypoalbuminemia on survival in patients with advanced inoperable esophageal cancer undergoing palliative treatment

Inflammation perpetuates individual tumor progression resulting in decreased survival in cancer patients. The aim of our study was to evaluate the influence of elevated levels of C‐reactive protein (CRP) as well as low levels of albumin on patients with inoperable esophageal carcinoma.

Resection in Stage I/II Non-Small Cell Lung Cancer

In spite of the developments in chemo- and radiotherapy, surgery remains the mainstay of curative treatment of early stage non-small cell lung cancer (NSCLC). In stage Ia/Ib (T1, T2, N0), NSCLC lobectomy offers the best chance for cure, yielding survival rates of between 58 and 76%. Since the extent of mediastinal lymph node dissection does not seem to play a major prognostic role in stage Ia, video-thoracoscopic lobectomy yields equally good results as the open approach. Due to the necessity for a small thoracotomy when harvesting the specimen and the time-consuming lymph-node dissection minimally invasive lobar resections have failed to become routinely used. Minor resections, though sometimes necessary from the functional point of view, have a lower curative potential. They yield the best results if applied in tumors measuring less than 2 cm. Stage II, characterized by involvement of the N1-position and/or a more central tumor growth, has a 5-year survival of 45-52% and requires treatment by lobectomy or pneumonectomy. Sleeve resection may obviate the need for pneumonectomy in central upper-lobe tumors. In interlobar N1, however, pneumonectomy is indicated from the oncological point of view, since even meticulous lymph-node dissection is unable to achieve tumor control in this situation.

Individualized, multimodal palliative treatment of inoperable esophageal cancer: Clinical impact of photodynamic therapy resulting in prolonged survival†

In esophageal carcinoma palliative treatment is often required due to advanced tumor stage or patient‐related factors. The main goal of our retrospective single center study was to evaluate the effect of an individualized multimodal palliative treatment, focusing on the efficacy of different treatment options.

Photodynamic Therapy of Non–Small Cell Lung Cancer. Narrative Review and Future Directions

Photodynamic therapy (PDT) is an established treatment modality for non-small cell lung cancer. Phototoxicity, the primary adverse event, is expected to be minimized with the introduction of new photosensitizers that have shown promising results in phase I and II clinical studies. Early-stage and superficial endobronchial lesions less than 1 cm in thickness can be effectively treated with external light sources. Thicker lesions and peripheral lesions may be amenable to interstitial PDT, where the light is delivered intratumorally. The addition of PDT to standard-of-care surgery and chemotherapy can improve survival and outcomes in patients with pleural disease. Intraoperative PDT has shown promise in the treatment of non-small cell lung cancer with pleural spread. Recent preclinical and clinical data suggest that PDT can increase antitumor immunity. Crosslinking of signal transducer and activator of transcription-3 molecules is a reliable biomarker to quantify the photoreaction induced by PDT. Randomized studies are required to test the prognosis value of this biomarker, obtain approval for the new photosensitizers, and test the potential efficacy of interstitial and intraoperative PDT in the treatment of patients with non-small cell lung cancer.

Hyperbaric oxygenation in the treatment of life-threatening isobutyl nitrite-induced methemoglobinemia--a case report.

Methemoglobinemia usually results from exposure to oxidizing substances such as nitrates or nitrites. Iron within hemoglobin is oxidized from the ferrous (Fe2+) state to the ferric (Fe3+) state, resulting in the inability to transport oxygen and carbon dioxide. Clinically, this condition causes functional cyanosis. As methemoglobin levels increase, patients show evidence of cellular hypoxia in all tissues. Death usually occurs when methemoglobin fractions approach 70% of total hemoglobin. We describe the case of a 35-year-old female patient with severe life-threatening isobutyl nitrite-induced methemoglobinemia of 75% of total hemoglobin. Toluidine-blue was administered as first-line antidotal therapy immediately, followed by hyperbaric oxygenation. The patient recovered uneventfully and could be discharged 3 days later.

Occult solitary submucosal jejunal metastasis from esophageal carcinoma

BackgroundMetastatic tumors of the intestinal tract from extra-abdominal sites are rare. In esophageal cancer, the liver, lung and the bones are the most common sites of metastases. Metastasis to intestines are very rare.Case presentationA 54-year old male was admitted with esophageal squamous cell carcinoma (SCC) associated with dysphagia II-III and weight loss of 20 kg. Preoperative routine staging failed to detect any metastases. A transthoracic esophagectomy and orthotopic gastric pull-up with collar esophago-gastrostomy, associated with 2-field lymphadenectomy was perfromed. During the digital placement of the naso-jejunal feeding catheter a submucosal jejunal nodule with a diameter of 1 cm, about 40 cm distal to the duodeno-jejunal fold was detected which was completely resected by jejunotomy. Histopathology of jejunal nodule showed metastasis from esophageal squamous cell carcinoma.ConclusionBecause of the extensic esophageal lymphatic system, an occult widespread dissemination of the tumor cells into the abdominal cavity is possible. Additional intraoperative evaluation of the small intestine and the complete abdominal cavity should be performed in every operation of esophageal carcinoma to detect possible occult intraabdominal metastases.