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In general, treatment for PanNET encompasses the same array of options as other neuroendocrine tumors, as discussed in that main article. However, there are some specific differences, which are discussed here.
In functioning PanNETs, octreotide is usually recommended prior to biopsy or surgery but is generally avoided in insulinomas to avoid profound hypoglycemia.
PanNETs in MEN1 are often multiple, and thus require different treatment and surveillance strategies.
Some PanNETs are more responsive to chemotherapy than are gastroenteric carcinoid tumors. Several agents have shown activity. In well differentiated PanNETs, chemotherapy is generally reserved for when there are no other treatment options. Combinations of several medicines have been used, such as doxorubicin with streptozocin and fluorouracil (5-FU) and capecitabine with temozolomide. Although marginally effective in well-differentiated PETs, cisplatin with etoposide has some activity in poorly differentiated neuroendocrine cancers (PDNECs), particularly if the PDNEC has an extremely high Ki-67 score of over 50%.
Several targeted therapy agents have been approved in PanNETs by the FDA based on improved progression-free survival (PFS):
- everolimus (Afinitor) is labeled for treatment of progressive neuroendocrine tumors of pancreatic origin in patients with unresectable, locally advanced or metastatic disease. The safety and effectiveness of everolimus in carcinoid tumors have not been established.
- sunitinib (Sutent) is labeled for treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease. Sutent also has approval from the European Commission for the treatment of 'unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors with disease progression in adults'. A phase III study of sunitinib treatment in well differentiated pNET that had worsened within the past 12 months (either advanced or metastatic disease) showed that sunitinib treatment improved progression-free survival (11.4 months vs. 5.5 months), overall survival, and the objective response rate (9.3% vs. 0.0%) when compared with placebo.
Treatment is by chemotherapy with streptozocin, dacarbazine, doxorubicin or by 'watchful waiting' and surgical debulking via Whipple procedure and other resections of the gastrointestinal organs affected.
Somatostatinoma is a malignant tumor of the delta cells of the endocrine pancreas that produces somatostatin. Increased levels of somatostatin inhibit pancreatic hormones and gastrointestinal hormones. Thus somatostatinomas are associated with mild diabetes mellitus (due to inhibition of insulin release), steatorrhoea and gallstones (due to inhibition of cholecystokinin release), and achlorhydria (due to inhibition of gastrin release). Somatostatinomas are commonly found in head of pancreas.
Pancreatic neuroendocrine tumors (PanNETs, PETs, or PNETs), often referred to as "islet cell tumors", or "pancreatic endocrine tumors" are neuroendocrine neoplasms that arise from cells of the endocrine (hormonal) and nervous system within the pancreas.
PanNETs are a type of neuroendocrine tumor, representing about one third of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Many PanNETs are benign, while some are malignant. Aggressive PanNET tumors have traditionally been termed "islet cell carcinoma".
PanNETs are quite distinct from the usual form of pancreatic cancer, the majority of which are adenocarcinomas, which arises in the exocrine pancreas. Only 1 or 2% of clinically significant pancreas neoplasms are PanNETs.
Treatment for FAP depends on the genotype. Most individuals with the APC mutation will develop colon cancer by the age of 40, although the less-common attenuated version typically manifests later in life (40–70). Accordingly, in many cases, prophylactic surgery may be recommended before the age of 25, or upon detection if actively monitored. There are several surgical options that involve the removal of either the colon or both the colon and rectum.
- Rectum involved: the rectum and part or all of the colon are removed. The patient may require an ileostomy (permanent stoma where stool goes into a bag on the abdomen) or have an ileo-anal pouch reconstruction. The decision to remove the rectum depends on the number of polyps in the rectum as well as the family history. If the rectum has few polyps, the colon is partly or fully removed and the small bowel (ileum) can be directly connected to the rectum instead (ileorectal anastomosis).
- Rectum not involved: the portion of the colon manifesting polyps can be removed and the ends 'rejoined' (partial colectomy), a surgery that has a substantial healing time, but leaves quality of life largely intact.
Prophylactic colectomy is indicated if more than a hundred polyps are present, if there are severely dysplastic polyps, or if multiple polyps larger than 1 cm are present.
Treatment for the two milder forms of FAP may be substantially different from the more usual variant, as the number of polyps are far fewer, allowing more options.
Various medications are being investigated for slowing malignant degeneration of polyps, most prominently the non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDS have been shown to significantly decrease the number of polyps but do not usually alter management since there are still too many polyps to be followed and treated endoscopically.
Prior to reaching the advanced stages of colorectal cancer, the polyps are confined to the inner wall and thickness of the intestinal tract and do not metastasize or 'spread'. So provided FAP is detected and controlled either at the pre-cancerous stage or when any cancerous polyps are still internal to the intestinal tract, surgery has a very high success rate of preventing or removing cancer, without recurrence, since the locations giving rise to cancer are physically removed "in toto" by the surgery.
Following surgery, if a partial colectomy has been performed, colonoscopic surveillance of the remaining colon is necessary as the individual still has a risk of developing colon cancer. However, if this happened, it would be a fresh incident from polyps developing anew in the unremoved part of the colon subsequent to surgery, rather than a return or metastasis of any cancer removed by the original surgery.
Periampullary cancer is a cancer that forms near the ampulla of Vater, an enlargement of the ducts from the liver and pancreas where they join and enter the small intestine.It consists of:
1. ampullary tumour from ampulla of Vater,
2. cancer of lower common bile duct, and
3. duodenal cancer adjacent to ampulla.
4. carcinoma head of pancreas
It presents with painless jaundice which may have waxing and waning nature because at times the sloughing of the tumor tissue relieves the obstruction partially.
Early treatment of an ectopic pregnancy with methotrexate is a viable alternative to surgical treatment which was developed in the 1980s. If administered early in the pregnancy, methotrexate terminates the growth of the developing embryo; this may cause an abortion, or the developing embryo may then be either resorbed by the woman's body or pass with a menstrual period. Contraindications include liver, kidney, or blood disease, as well as an ectopic embryonic mass > 3.5 cm.
Also, it may lead to the inadvertent termination of an undetected intrauterine pregnancy, or severe abnormality in any surviving pregnancy. Therefore, it is recommended that methotrexate should only be administered when hCG has been serially monitored with a rise less than 35% over 48 hours, which practically excludes a viable intrauterine pregnancy.
If bleeding has already occurred, surgical intervention may be necessary. However, whether to pursue surgical intervention is an often difficult decision in a stable patient with minimal evidence of blood clot on ultrasound.
Surgeons use laparoscopy or laparotomy to gain access to the pelvis and can either incise the affected Fallopian and remove only the pregnancy (salpingostomy) or remove the affected tube with the pregnancy (salpingectomy). The first successful surgery for an ectopic pregnancy was performed by Robert Lawson Tait in 1883. It is estimated that an acceptable rate of PULs that eventually undergo surgery is between 0.5 and 11%.
Autotransfusion of a woman's own blood as drained during surgery may be useful in those who have a lot of bleeding into their abdomen.
Published reports that a re-implanted embryo survived to birth were debunked as false.
Drugs that increase serotonin signalling in the brain slow ejaculation and have been used successfully to treat PE. These include selective serotonin reuptake inhibitors (SSRIs), such as paroxetine or dapoxetine, as well as clomipramine. Ejaculatory delay typically begins within a week of beginning medication. The treatments increase the ejaculatory delay to 6–20 times greater than before medication. Men often report satisfaction with treatment by medication, and many discontinue it within a year. However, SSRIs can cause various types of sexual dysfunction such as anorgasmia, erectile dysfunction, and diminished libido.
Dapoxetine is a short-acting SSRI which appears to work when taken as needed for PE. It is generally well tolerated. Tramadol, an atypical oral analgesic, appears to be effective.
Desensitizing topical medications like lidocaine that are applied to the tip and shaft of the penis can also be used. These are applied "as needed", 10–15 minutes before sexual activity and have fewer potential systemic side effects as compared to pills. Use of topicals is sometimes disliked due to the reduction of sensation in the penis as well as for the partner (due to the medication rubbing onto the partner).
Several treatments have been tested for treating premature ejaculation. A combination of medication and non-medication treatments is often the most effective method.
Animal models using mammals and invertebrates have been informative in studying the effects of ethanol on not only pharmacokinetics of alcohol but also pharmacodynamics, in particular in the nervous system. Ethanol-induced intoxication is not uncommon in the animal kingdom, as noted here:
More recently, studies using animal models have begun to elucidate the effects of ethanol on the nervous system. Traditionally, many studies have been performed in mammals, such as mice, rats, and non-human primates. However, non-mammalian animal models have also been employed; in particular, the Ulrike Heberlein group at UC San Francisco has used "Drosophila melanogaster", the fruit fly, taking advantage of its facile genetics to dissect the neural circuits and molecular pathways, upon which ethanol acts. The series of studies carried in the Heberlein lab has identified insulin and its related signaling pathways as well as biogenic amines in the invertebrate nervous system as being important in alcohol tolerance. The value of antabuse (disulfiram) as a treatment for alcoholism has been tested using another invertebrate animal model, the honey bees. It is important to note that some of the analogous biochemical pathways and neural systems have been known to be important in alcohol's effects on humans, while the possibility that others may also be important remains unknown. Research of alcohol's effects on the nervous system remains a hot topic of research, as scientists inch toward understanding the problem of alcohol addiction.
In addition to the studies carried out in invertebrates, researchers have also used vertebrate animal models to study various effects of ethanol on behaviors.
The short-term effects of alcohol (also known formally as ethanol) consumption–due to drinking beer, wine, distilled spirits or other alcoholic beverages–range from a decrease in anxiety and motor skills and euphoria at lower doses to intoxication (drunkenness), stupor, unconsciousness, anterograde amnesia (memory "blackouts"), and central nervous system depression at higher doses. Cell membranes are highly permeable to alcohol, so once alcohol is in the bloodstream it can diffuse into nearly every cell in the body.
The concentration of alcohol in blood is measured via blood alcohol content (BAC). The amount and circumstances of consumption play a large part in determining the extent of intoxication; for example, eating a heavy meal before alcohol consumption causes alcohol to absorb more slowly. The amount of alcohol consumed largely determines the extent of hangovers, although hydration also plays a role. After excessive drinking, stupor and unconsciousness can occur. Extreme levels of consumption can lead to alcohol poisoning and death (a concentration in the blood stream of 0.40% will kill half of those affected). Alcohol may also cause death indirectly, by asphyxiation from vomit.
Alcohol can greatly exacerbate sleep problems. During abstinence, residual disruptions in sleep regularity and sleep patterns are the greatest predictors of relapse.