Surgery Updates

·         A foundational principle of the medical tradition is to do no harm: primum non nocere. In 2000, a widely publicized report from the Institute of Medicine, To Err is Human, estimated that 98,000 people die each year in U.S. hospitals as a result of medical injuries. This report, among others already in the literature, led to the creation of a number of national quality improvement projects that were specifically designed to improve surgical care in hospitals. One of the best known is the Surgical Care Improvement Project (SCIP), part of a national campaign aimed at reducing surgical complications by 25% by 2010.

·         An emerging and still controversial indication for circumcision is in the prevention of sexually acquired human immunodeficiency virus (HIV) infection in communities where this disease is common; large clinical trials have recently shown that circumcision reduces the risk of HIV transmission.

·         Recent myocardial infarction is a strong contraindication to elective anaesthesia. There is a significant mortality rate from anaesthesia within 3 months of infarction and elective procedures should ideally be delayed until at least 6 months have elapsed.

·         Recently, the British Association of Parenteral and Enteral Nutrition introduced a Malnutrition Universal Screening Tool (MUST), which is a fivestep screening tool to identify adults who are malnourished or at risk of undernutrition. Takes into account BMI, Wt LOSS IN 3-6 months and ACUTE DISEASE EFFECT.

·         Recent reports of tumour implantation in the locations of port sites have raised important questions about the future of the laparoscopic treatment of malignancy.

·         Recently, an interspinous process decompression system (X-stop) has been found to be effective for patients suffering from lumbar spinal stenosis when compared with non-operative therapy.

·         Femoroacetabular impingement (FAI) has been proposed as an aetiological factor responsible for the development of primary osteoarthritis. The theory is based on the observation that, in certain hips with aberrant morphological features, an abnormal contact occurs between the proximal femur and the acetabular rim during the terminal range of movement, leading to lesions of the acetabular labrum and/or the adjacent acetabular cartilage. This type of repetitive abutment in due course leads to progressive loss of the articular cartilage and labral lesions because of a sheering stress, resulting in degenerative joint disease if the underlying cause is not addressed.

·         E-thrombosis has been used to describe blood clots occurring in people sitting at their computers for long periods of time.

·         A recent technique known as transanal endoscopic microsurgery (TEM) has been developed (Buess), which has improved the endoanal approach for the local removal of villous adenomas. The method requires the insertion of a large operating sigmoidoscope. The rectum is distended by carbon dioxide insufflation, the operative field is magnified by a camera inserted via the sigmoidoscope, and the image is displayed on a monitor. The lesion is excised using specially designed instruments. The technique is highly specialised and takes a considerable amount of time to master.

·         Non-heart-beating (asystolic) donors

There is an increasing use of kidneys and more recently livers from non-heart-beating (asystolic) donors (NHBD) in an attempt to address the shortage of organs for transplantation. Kidneys may be procured from patients who are dead on arrival at the hospital or who have died after withdrawal of support or following unsuccessful resuscitation. NHBD can be grouped according to the Maastricht classification as follows:

• category 1: dead on arrival at hospital;

• category 2: unsuccessful resuscitation in hospital;

• category 3: ‘awaiting cardiac arrest’ after withdrawal of support;

• category 4: cardiac arrest while brain dead.

Maastricht category 1 and 2 donors are sometimes referred to as uncontrolled NHBD.

·         Intradiscal electrothermal therapy (IDET) was heralded as a new treatment for patients with discographically proven discogenic low back pain. There are two randomized controlled trials assessing the efficacy of IDET. The first showed modest overall benefit, and the second showed IDET to be no more effective than placebo for the treatment of chronic discogenic low back pain.

·         One study has suggested an association between Candida sepsis and ROP in extremely-low-birth-weight infants. The study found increased severity of ROP and need for laser therapy after candidal infection.

·         The recently introduced Harmonic Scalpel is an instrument that cuts and coagulates tissue via vibration at 55 kHz. The device converts electrical energy into mechanical motion. The motion of the blade causes collagen molecules within the tissue to become denatured forming a coagulum. There is no significant electrical current that flows through the patient. The instrument has proved advantageous in performing thyroidectomy, hemorrhoidectomy, transsection of the short gastric veins during splenectomy, and in transecting hepatic parenchyma.

·         Drotracogin alpha (activated), also known as Xigris, is a recombinant form of human-activated protein C. The use of this agent in a series of patients with sepsis syndrome has been associated with a 6% overall reduction in mortality

·         The AIS is a list which assigns a number from 1 (minor injury) to 6 (always fatal) for the various spectrum of organ injuries. The Injury Severity Score (ISS) was devised to address this concern. The ISS is calculated by squaring the AIS from the three worst injured of six body compartments (head and neck, face, chest, abdomen and pelvis, extremities, and external) and adding them together. Scores can range from 0 to 75. The Revised Trauma Score (RTS) is most commonly used today. It is calculated from the GCS, blood pressure, and respiratory rate, with the GCS being most heavily weighted. The RTS is a purely physiologic score which is compromised by the relative insensitivity of these common clinical measurements. More recently, the TRISS method (Trauma and Injury Severity Score) was developed to incorporate both the RTS and ISS, thereby combining physiologic and anatomic scores, as well as enhancing the importance of head injury. Unfortunately, TRISS remains fundamentally flawed because of the limitations of RTS and ISS. Newer versions of the TRISS concept, such as ASCOT (A Severity Characterization of Trauma), have also failed to improve the prediction of postinjury mortality.

·         Recently, serum procalcitonin has been shown to be a sensitive marker of significant infection in burn patients.

·         main effect of arginine on wound healing is to enhance wound collagen deposition. Recently, a dietary supplemental regimen of arginine, β-hydroxy-β-methyl butyrate, and glutamine was found to significantly and specifically enhance collagen deposition in elderly, healthy human volunteers when compared to an isocaloric, isonitrogenous supplement

·         High-throughput technologies such as matrix-assisted laser-desorption-ionization time of flight (MALDI-TOF) mass spectroscopy and liquid chromatography-ion-spray tandem mass spectroscopy (LC-MS/MS) have revolutionized the field of proteomics and are now being used to compare serum protein profiles between patients with cancer and individuals without cancer.Recently, investigators have compared the proteomic profiles of patients with prostate cancer and ovarian cancer to those of controls, identifying unique proteins in the sera of cancer patients.Identification of unique proteins as well as unique proteomic profiles for most cancer types is being pursued actively by many researchers, which if successful, could dramatically enhance our ability to detect cancers early.

·         The most commonly used device for VSD Closure is the Amplatzer septal occluder (AGA Medical Corp, MN) device, which is a Nitinol metal mesh device, placed percutaneously and delivered with echo and fluoroscopic guidance.

·         Aortic Valve Repair Technique: Ross, David, Yacoub, and Casselman

·         An association between PAD and hypertriglyceridemia has been reported, but the strength of this association is unclear. Recently, it has been shown that Lp(a) is a significant independent risk factor for PAD.

·         Clagett has popularized the use of bilateral superficial femoral vein to replace infected aortic grafts. This technique can also be useful for treatment of mycotic aneurysms.

·         The benefit of carotid endarterectomy for patients with symptomatic cerebrovascular disease has recently been established by both the ECST and NASCET trials.

·         An intraluminal electrical impedance catheter has recently been developed for the measurement of gastrointestinal function. Impedance is the ratio of voltage to current, and is a measure of the electrical conductivity of a hollow organ and its contents. Intraluminal electrical impedance is inversely proportional to the electrical conductivity of the luminal contents and the cross-sectional area of the lumen. Air has a very low electrical conductivity and therefore high impedance. Saliva and food cause an impedance decrease because of their increased conductivity. Luminal dilatation results in a decrease in impedance, whereas luminal contraction yields an impedance increase. Investigators to date have established the impedance waveform characteristics that define esophageal bolus transport. This allows for the characterization of both esophageal function, via quantification of bolus transport, and gastroesophageal reflux.

·         Recently it has been noted that the anorexic hormone leptin, secreted mostly by fat but also by gastric mucosa, inhibits gastric emptying, perhaps through the same pathway as CCK (which also has properties of a satiety hormone). The orexic hormone ghrelin has opposite effect.

·         GLP-2 both stimulates cellular proliferation and inhibits apoptosis in the intestinal epithelium. It has been demonstrated to induce intestinal regeneration and promote healing in numerous experimental models of intestinal disease. It is currently under clinical evaluation as an intestinotrophic agent in patients suffering from the short bowel syndrome, as discussed later under "Short-Bowel Syndrome."

·         serial transverse enteroplasty procedure (STEP) was described for SBS. This procedure is designed to accomplish lengthening of dilated small intestine without the need for separating its dual vasculature

·         PET using H2(15)O has recently been shown to be a noninvasive method to measure portal venous and hepatic arterial blood flow.

·         Pancreastatin is a recently discovered pancreatic islet peptide product that inhibits insulin, and possibly somatostatin release, and augments glucagon release.In addition to this effect on the endocrine pancreas, pancreastatin inhibits pancreatic exocrine secretion.

·         mutations in cationic trypsinogen gene PRSS1, which results in pancreatitis.

·         The measurement of IL-6 has recently been shown to distinguish patients with mild or severe forms of the Acute Pancreatitis. Another prognostic marker under evaluation is urinary-trypsinogen activation peptide (TAP). TAP is a five- to seven-amino acid peptide that is released from the N-terminus of trypsinogen during its activation.

·         The recently identified protein pendrin is thought to mediate iodine efflux at the apical membrane of Thyroid Follicle.

·         Recently, salivary cortisol measurements using commercially available kits also have demonstrated superior sensitivity in diagnosing Cushing's syndrome. However, they are not used routinely.

·         Current resuscitation algorithms are based on the sequence of crystalloid followed by red blood cells and then plasma and platelet transfusions and have been in widespread use since the 1970s. Recently, the damage control resuscitation (DCR) strategy, aimed at halting and/or preventing rather than treating the lethal triad of coagulopathy, acidosis, and hypothermia, has challenged traditional thinking on early resuscitation strategies.

·         Following direct tissue injury or infection, there are several mechanisms that lead to the activation of the active inflammatory and immune responses. These include release of bioactive peptides by neurons in response to pain and the release of intracellular molecules by broken cells, such as heat shock proteins, mitochondrial peptides, heparan sulfate, high mobility group box 1, and RNA. Only recently has it been realized that the release of intracellular products from damaged and injured cells can have paracrine and endocrine-like effects on distant tissues to activate the inflammatory and immune responses. This hypothesis, which was first proposed by Matzinger, is known as danger signaling. Under this novel paradigm of immune function, endogenous molecules are capable of signaling the presence of danger to surrounding cells and tissues. These molecules that are released from cells are known as damage associated molecular patterns (DAMPs). DAMPs are recognized by cell surface receptors to effect intracellular signaling that primes and amplifies the immune response. These receptors are known as pattern recognition receptors (PRRs) and include the Toll-like receptors (TLRs) and the receptor for advanced glycation end products. Interestingly, TLRs and PRRs were first recognized for their role in signaling as part of the immune response to the entry of microbes and their secreted products into a normally sterile environment. These bacterial products, including lipopolysaccharide, are known as pathogen-associated molecular patterns. The salutary consequences of PRR activation most likely relate to the initiation of the repair process and the mobilization of antimicrobial defenses at the site of tissue disruption. However, in the setting of excessive tissue damage, the inflammation itself may lead to further tissue damage amplifying the response both at the local and systemic level. PRR activation leads to intracellular signaling and release of cellular products including cytokines.

·         The use of corticosteroids in the treatment of sepsis and septic shock has been controversial for decades. The observation that severe sepsis often is associated with adrenal insufficiency or glucocorticoid receptor resistance has generated renewed interest in therapy for septic shock with corticosteroids. A single IV dose of 50 mg of hydrocortisone improved mean arterial blood pressure response relationships to norepinephrine and phenylephrine in patients with septic shock, and was most notable in patients with relative adrenal insufficiency. A more recent study evaluated therapy with hydrocortisone (50 mg IV every 6 hours) and fludrocortisone (50 g orally once daily) vs. placebo for 1 week in patients with septic shock.⁸⁴ As in earlier studies, the authors performed corticotropin tests on these patients to document and stratify patients by relative adrenal insufficiency. In this study, 7-day treatment with low doses of hydrocortisone and fludrocortisone significantly and safely lowered the risk of death in patients with septic shock and relative adrenal insufficiency. In an international, multicenter, randomized trial of corticosteroids in sepsis (CORTICUS study; 499 analyzable patients), steroids showed no benefit in intent to treat mortality or shock reversal.⁸⁵ This study suggested that hydrocortisone therapy cannot be recommended as routine adjuvant therapy for septic shock. However, if SBP remains less than 90 mmHg despite appropriate fluid and vasopressor therapy, hydrocortisone at 200 mg/day for 7 days in four divided doses or by continuous infusion should be considered.

·         Right ventricular end-diastolic volume index (RVEDVI) seems to more accurately predict preload for cardiac index than does pulmonary artery wedge pressure.¹¹⁰ Chang and colleagues reported that 50% of trauma patients had persistent splanchnic ischemia that was reversed by increasing RVEDVI. RVEDVI is a parameter that seems to correlate with preload-related increases in cardiac output. More recently, these authors have described left ventricular power output as an endpoint (LVP >320 mmHg·L/min per square meter), which is associated with improved clearance of base deficit and a lower rate of organ dysfunction following injury.

·         Natural orifice transluminal endoscopic surgery (NOTES) is a recent extension of interventional endoscopy. Using the mouth, the anus, the vagina, and the urethra (natural orifices), flexible endoscopes are passed through the wall of the esophagus, stomach, colon, bladder, or vagina entering the mediastinum, the pleural space, or the peritoneal cavity. The advantage of this method of minimal access is principally the elimination of the scar associated with laparoscopy or thoracoscopy. Other advantages are yet to be elucidated, including pain reduction, need for hospitalization, and cost savings. The first case of transvaginal removal of a normal appendix has recently been reported.

·         The anabolic steroid oxandrolone has been extensively studied in pediatric patients as well, and has demonstrated improvements in lean body mass and bone density in severely burned children.¹⁰⁰ The weight gain and functional improvements seen with oxandrolone may persist even after stopping administration of the drug.¹⁰¹ A recent double-blinded, randomized study of oxandrolone showed decreased length of stay, improved hepatic protein synthesis, and no adverse effects on the endocrine function, although the authors noted a rise in transaminases with unclear clinical significance

·         Recently, a dietary supplemental regimen of arginine, -hydroxy--methylbutyrate, and glutamine was found to significantly and specifically enhance collagen deposition in elderly, healthy human volunteers when compared to an isocaloric, isonitrogenous supplement. As increases in breaking strength during the first weeks of healing are directly related to new collagen synthesis, arginine supplementation may result in an improvement in wound strength as a consequence of enhanced collagen deposition.

·         Germline mutations in the hCHK2 gene have recently been identified as another susceptibility gene for LFS. The hCHK2 gene encodes for the human homologue of the yeast Cds1 and the RAD53 G₂ checkpoint, whose activation by DNA damage prevents entry into mitosis. CHK2 directly phosphorylates p53, which suggests that CHK2 may be involved in p53 regulation after DNA damage. CHK2 also regulates BRCA1 function after DNA damage. The protein truncation mutation 1100delC in exon 10 identified in LFS and breast cancer abolishes the kinase function of CHK2. Another reported mutation in hCHK2 is a missense mutation (R145W) that destabilizes the protein, shortening its half-life.

·         The prognostic implications of detection of CTCs by RT-PCR have been intensively studied for melanoma. In the recent multicenter Sunbelt Melanoma Trial, serial RT-PCR was performed on peripheral blood samples using four markers—tyrosinase, melanoma antigen reacting to T cell (MART-1), melanoma antigen 3 (MAGE3), and gp 100—to detect occult melanoma cells in the bloodstream.⁹⁸ Although there were no differences in survival between patients in whom at least one marker was detected and those in whom no markers were detected, the disease-free survival and distant disease-free survival were worse for patients in whom more than one marker was detected at any time during follow-up.⁹⁸ The detection of occult cancer cells with RT-PCR remains investigational, however, and is not used to direct therapy for melanoma and other cancer types at this time.

·         Comparisons of the mAb directed against the alpha chain of LFA-1 (odulimomab) with antithymocyte immunoglobulin as induction therapy found, at 3 and 12 months after transplantation, similar rate and severity of rejection episodes as well as incidence of infection. An anti–LFA-1 mAb (efalizumab) was found capable of inhibiting lymphocyte adhesion, circulation, and activation. Another potential benefit of anti-LFA mAbs observed in both animal models and human beings is that they can diminish the ischemia-reperfusion injury associated with delayed graft function. The anti-CD4 mAb (priliximab) already has shown immunosuppressive potential in some therapeutic pilot studies.

·         A recent advance in EEG monitoring is the use of the bispectral index (BIS) to titrate the level of sedative medications. Although sedative drugs usually are titrated to the clinical neurologic examination, the BIS device has been used in the operating room to continuously monitor the depth of anesthesia. The BIS is an empiric measurement statistically derived from a database of more than 5000 EEGs.⁸⁸ The BIS is derived from bifrontal EEG recordings and analyzed for burst suppression ratio, relative alpha:beta ratio, and bicoherence. Using a multivariate regression model, a linear numeric index (BIS) is calculated, ranging from 0 (isoelectric EEG) to 100 (fully awake). Its use has been associated with lower consumption of anesthetics during surgery and earlier awakening and faster recovery from anesthesia.⁸⁹ The BIS also has been validated as a useful approach for monitoring the level of sedation for ICU patients, using the revised Sedation-Agitation Scale as a gold standard.

·         Esophageal Impedance:

An intraluminal electrical impedance catheter has recently been developed for the measurement of GI function. Impedance is the ratio of voltage to current, and is a measure of the electrical conductivity of a hollow organ and its contents. Intraluminal electrical impedance is inversely proportional to the electrical conductivity of the luminal contents and the cross-sectional area of the lumen. Air has a very low electrical conductivity and, therefore, high impedance. Saliva and food cause an impedance decrease because of their increased conductivity. Luminal dilatation results in a decrease in impedance, whereas luminal contraction yields an impedance increase.

Esophageal impedance has been validated as an appropriate method for the evaluation of GI function and is becoming increasingly used for the diagnosis of gastroesophageal reflux.

Impedance pH may be particularly useful in evaluating patients with persistent symptoms despite PPI treatment, patients with respiratory symptoms, and postoperative patients who are having symptoms that are elusive to diagnosis

·         The recent development of a wireless capsule, which can be implanted in the esophagus and record pH data for 48 hours, has significantly changed patient satisfaction with the procedure.

The Bravo pH Capsule (Medtronics, Minneapolis, Minn) measures pH levels in the esophagus and transmits continuous esophageal pH readings to a receiver worn on the patient's belt or waistband.  Symptoms that the patient experiences are recorded in a diary and/or by pressing buttons on the receiver unit. Generally, 48 hours of pH data are measured with this probe. A recent study has shown that the addition of a second day of pH monitoring increased the sensitivity of pH measurement by 22%. The capsule eventually detaches and passes through the digestive tract in 5 to 7 days.

·         The MammaPrint test was recently approved by the FDA for use in patients with newly diagnosed, node-negative breast cancer. The MammaPrint test is based on a 70-gene profile, and fresh tissue is required to perform the assay. The Oncotype DX assay is performed using paraffin-embedded tumor tissue and therefore can be carried out on archived samples.

·         Desmoid tumors have recently been shown to possess alterations in the adenomatous polyposis coli/-catenin pathway, and cyclin D1 dysregulation is thought to play a significant role in their pathogenesis.¹²⁹ Associations with other diseases and conditions are well documented, especially those with similar alterations in the adenomatous polyposis coli pathway, such as familial adenomatous polyposis (Gardner's syndrome). Other conditions with increased risk of desmoid tumor formation include states of increased estrogen levels (pregnancy) and trauma. Surgical incisions (abdominal and thoracic) have been the site of desmoid development, either in or near the scar.

·         Zero-balance ultrafiltration (Z-BUF) is a method of ultrafiltration during CPB. This technique removes significant amounts of inflammatory mediators associated with CPB and potentially attenuates the adverse effects of bypass while maintaining the patient's volume status. Recent studies have shown that Z-BUF reduces pulmonary edema and protects against lung injury.⁶ Additionally, the use of Z-BUF has been shown to decrease the concentrations of interleukin-6 and interleukin-8 that are markers of systemic inflammation associated with CPB.

·         A total artificial heart (TAH) will be the conceptual end solution for cardiac replacement of the failing heart. This technology has moved in a vastly different direction than VADs. Assist devices work in parallel to the left ventricle, and are becoming simpler, smaller, and valveless, in contrast to the TAH, which displaces the heart and retains pulsatile flow. The original Jarvik TAH is still in use as the CardioWest BiVAD and is used as a bridge to transplant. More recently, the AbioCor TAH has been implanted as part of an FDA trial and recently obtained FDA Humanitarian Device Exemption approval in 2006.

·         Loeys-Dietz syndrome is phenotypically distinct from Marfan syndrome. It is characterized as an aneurysmal syndrome with widespread systemic involvement. Loeys-Dietz syndrome is an aggressive, autosomal dominant condition that is distinguished by the triad of arterial tortuosity and aneurysms, hypertelorism (widely spaced eyes), and bifid uvula or cleft palate. It is caused by heterozygous mutations in the genes encoding TGF- receptors, rather than fibrillin 1.

·         Unfortunately, laboratory studies are of little help in diagnosing acute aortic dissection. There has been recent interest in using D-dimer level to aid in making this diagnosis. Several reports have demonstrated that D-dimer is an extremely sensitive indicator of acute aortic dissection; elevated levels are found in approximately 97% of affected patients.

·         However, the majority of TIAs resolve within minutes, and longer lasting neurologic deficits more likely represent a stroke. Recently, the term brain attack has been coined to refer to an acute stroke or TIA, denoting the condition as a medical emergency requiring immediate attention, similar to a heart attack.

·         Recently, it has been noted that the anorexigenic hormone leptin, secreted mostly by fat but also by gastric mucosa, inhibits gastric emptying, perhaps through the same pathway as CCK (which also has properties of a satiety hormone). The orexigenic hormone ghrelin has the opposite effect

·         There are two clinical syndromes characterized by epithelial hyperplasia and giant gastric folds: ZES and Ménétrier's disease. The latter is characteristically associated with protein-losing gastropathy and hypochlorhydria. There are large rugal folds in the proximal stomach, and the antrum is usually spared. Mucosal biopsy shows diffuse hyperplasia of the surface mucus-secreting cells and usually decreased parietal cells. It has recently been suggested that Ménétrier's disease is caused by local overexpression of transforming growth factor alpha in the gastric mucosa, which stimulates the epidermal growth factor receptor, a receptor tyrosine kinase, on gastric SECs. This results in the selective expansion of surface mucous cells in the gastric body and fundus. A few patients with this unusual disease have been successfully treated with the epidermal growth factor receptor blocking monoclonal antibody cetuximab.

·         AFAP (Attenuated FAP) is a recently recognized variant of FAP associated with mutations at the 3' or 5' end of the APC gene. Patients present later in life with fewer polyps (usually 10 to 100) dominantly located in the right colon, when compared to classic FAP. Colorectal carcinoma develops in more than 50% of these patients, but occurs later (average age 55 years). Patients are also at risk for duodenal polyposis. However, in contrast to FAP, APC gene mutations are present in only about 30% of patients with AFAP. When present, these mutations are expressed in an autosomal dominant pattern.

·         Recent studies have shown that a fifth islet peptide, ghrelin, is secreted from a distinct population of islet cells, called epsilon cells.^15,16 Ghrelin also is present in the gastric fundus in large amounts and stimulates growth hormone secretion via growth hormone releasing hormone release from the pituitary. It is an orexigenic, or appetite-stimulating, peptide the plasma levels of which are increased in obesity. Ghrelin has also been shown to block insulin effects on the liver, and inhibits the -cell response to incretin hormones and glucose.¹⁷ Therefore, ghrelin secretion from and within the islet may modulate the responses of other islet cells to nutrient and hormonal stimuli.

Amylin or islet amyloid polypeptide (IAPP) is a 37-amino-acid polypeptide that was discovered in 1988. IAPP is predominantly expressed by the pancreatic -cells, where it is stored along with insulin in secretory granules.¹⁸ The function of IAPP seems to be the modulation or counterregulation of insulin secretion and function. Pancreastatin is a recently discovered pancreatic islet peptide product that inhibits insulin, and possibly somatostatin release, and augments glucagon release

·         Recent studies also indicate that Toll-like receptor 4 (TLR4) is significant in determining the severity of acute pancreatitis. The TLR4 initiates a complex signaling pathway when it interacts with lipopolysaccharides that result in a proinflammatory response. Mice in which TLR4 is genetically deleted have significantly reduced pancreatitis; this suggests that TLR4 is a significant promoter of proinflammation. However, this effect appears independently of lipopolysaccharides and is probably mediated by a hitherto unknown TLR4 agonist. It is likely that TLR4 antagonists would be a good therapy against pancreatitis.

·         A recently identified protein, pendrin, is thought to mediate iodine efflux at the apical membrane of thyrocyte.