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[Thyroid nodule].
The thyroid nodule is a frequent, most often benign, chronic, multifocal and slowly progressive disease. The first line strategy is to diagnose cancerous nodules (<5%) and relies upon fine needle aspiration (FNA), a specialised technique which in trained hands has a false negative rate of below 5%. The interest to explore small thyroid nodules is controversial since the prognosis of thyroid cancer is excellent for lesions measuring less than 20 mm. Though imaging accuracy is quite limited in assessing the diagnosis of thyroid cancer, both ultrasounds (US) and thyroid scan are helpful to enhance nodular identification (>30%), to sort the nodules relevant for cytological sampling and to optimize the follow-up, the major source of health costs. Suspicious and non contributive FNAs must have a control FNA within 6 months. Nodules with a non suspicious FNA (>85%) require long term follow-up. This follow-up is mainly morphological. New or evolutive nodules, as assessed by palpation or US, will require iterative FNAs or should be considered for surgery. In patients with hyperfunctioning nodules on the scan (10 to 20%), a yearly evaluation of the TSH level is sufficient. These nodules account either for autonomously functioning ones, which slowly develop towards thyrotoxicosis, or for hyperplastic nodules frequently disclosing a lymphocytic thyroiditis. Morbidity due to thyroid autonomy is still underestimated especially in aging patients with TSH levels < or =0.60 mU/L. An algorithmic approach to the diagnostic and follow-up evaluation of thyroid nodule is suggested.
Comparison of the effects of propofol and midazolam on the cardiovascular autonomic nervous system during combined spinal and epidural anesthesia.
STUDY OBJECTIVE: To investigate the effect of propofol and midazolam on cardiac autonomic nervous system (CANS) activity during combined spinal-epidural anesthesia. DESIGN: Prospective, clinical study. SETTING: Operating room of a university hospital. PATIENTS: Forty ASA physical status I and II patients scheduled for knee surgery. INTERVENTION: Patients were randomized to receive sedation with either propofol or midazolam. MEASUREMENTS: Heart rate (HR), HR variability (HRV), systolic arterial pressure (SAP), and SAP variability (SAPV) were used for the analysis. These values were measured at the preanesthetic period, after intrathecal injection for spinal anesthesia, after sedation with propofol or midazolam, and just before the end of surgery with sedation. Cross-spectral analyses of the HR and SAP data were assessed to quantify the frequency-related coherence spectra and phase spectra. MAIN RESULTS: Spinal anesthesia itself had no effect on power spectral changes in both groups. After sedation, as for HRV, high-frequency (HF) power (HF, 0.15-0.40 Hz) did not change, whereas low-frequency (LF) power (LF, 0.04-0.15 Hz) and LF/HF, an indicator of CANS balance, significantly decreased with propofol. Further, coherence in cross-spectra presented depression in the LF band area after sedation with propofol. Before the end of surgery with sedation, LF and LF/HF in both HRV and SAPV were correlated with age in those with propofol; however, scarce relation was observed in those who received midazolam. CONCLUSIONS: Propofol was more potent than midazolam in causing CANS activity to be sympatholytic during combined spinal and epidural anesthesia and which was correlated with age only with propofol.
Nociceptive and anaesthetic-induced changes in pulse transit time during general anaesthesia.
BACKGROUND: Pulse transit time (rPTT), the interval between ventricular electrical activity and arrival of a peripheral pulse waveform, has been used to detect changes in autonomic tone. The aim of this observational pilot study was to measure changes in rPTT in response to general anaesthesia and noxious stimuli. METHODS: Thirty-one healthy women undergoing gynaecological surgery were allocated to groups depending on the need for airway management with tracheal intubation (n=9), a laryngeal mask (LMA, n=17) or a facemask (n=5). During general anaesthesia, we measured changes in RR interval (RR-int) and rPTT after (i) induction of anaesthesia, (ii) airway manipulation and (iii) surgical stimulus. rPTT was estimated as the interval from the peak in the R-wave to detection of the pulse oximeter waveform in the periphery. RESULTS: Mean baseline rPTT was 245 (SD 27) ms. Upon induction of anaesthesia, rPTT increased (by 28.2 (20.4) ms, P<0.001) in all but two patients. rPTT decreased in response to endotracheal intubation (by 43.1 (24.6) ms, P=0.001) but did not vary in response to insertion of LMA or surgical stimulus. Mean baseline RR-int was 865 (141) ms. A mean reduction in RR-int after tracheal intubation did not reach statistical significance. RR-int was unchanged with induction of anaesthesia, LMA insertion or surgical stimulus. CONCLUSION: Variation in rPTT reflects autonomic responses to nociceptive stimulation and fluctuations in anaesthetic depth independently of heart rate.
[Autonomous thyroid nodule: relations between clinical symptomatology and goiter endemia].
Sixty-three patients with autonomous thyroid nodule were studied, thirty-five from an endemic goiter area (EA) and twenty-eight from a non-endemic goiter area (NEA). Clinical history, physical examination, ultrasonography, thyroid hormone levels, and fine needle aspiration (FNA), were utilized to investigate whether or not iodine deficiency determined differences in the latency of progression to toxicity, the seriousness of illness and thyroid hormone levels. No significant difference was observed in the age of onset of nodularity, while the latency of progression to toxicity was significantly decreased in the EA (p less than 0.001). The ultrasonographic pattern did not show significant volume variations between the EA and NEA, but there was a slight prevalence of multinodular lesions in EA. No significant difference in serum thyroid hormone levels was found between the two areas in non toxic patients, while at the onset of hyperthyroidism higher levels of FT were observed in the EA than in the NEA. FNA showed a prevalence of colloid lesions in EA, while hyperplastic lesions prevail in the NEA. Forty-two patients underwent surgery: the extent of surgery was greater in patients from the EA. In conclusion, in iodine deficient areas earlier clinical thyrotoxicosis and a higher prevalence of hypoactive thyroid nodules were observed. Furthermore, in EA, the autonomous nodule in non toxic phase is more frequently associated with colloid lesions than hyperplastic lesions.
Structural effects and potential changes in growth factor signalling in penis-projecting autonomic neurons after axotomy.
BACKGROUND: The responses of adult parasympathetic ganglion neurons to injury and the neurotrophic mechanisms underlying their axonal regeneration are poorly understood. This is especially relevant to penis-projecting parasympathetic neurons, which are vulnerable to injury during pelvic surgery such as prostatectomy. We investigated the changes in pelvic ganglia of adult male rats in the first week after unilateral cavernous (penile) nerve axotomy (cut or crush lesions). In some experiments FluoroGold was injected into the penis seven days prior to injury to allow later identification of penis-projecting neurons. Neurturin and glial cell line-derived neurotrophic factor (GDNF) are neurotrophic factors for penile parasympathetic neurons, so we also examined expression of relevant receptors, GFRalpha1 and GFRalpha2, in injured pelvic ganglion neurons. RESULTS: Axotomy caused prolific growth of axon collaterals (sprouting) in pelvic ganglia ipsilateral to the injury. These collaterals were most prevalent in the region near the exit of the penile nerve. This region contained the majority of FluoroGold-labelled neurons. Many sprouting fibres formed close associations with sympathetic and parasympathetic pelvic neurons, including many FluoroGold neurons. However immunoreactivity for synaptic proteins could not be demonstrated in these collaterals. Preganglionic terminals showed a marked loss of synaptic proteins, suggesting a retrograde effect of the injury beyond the injured neurons. GFRalpha2 immunofluorescence intensity was decreased in the cytoplasm of parasympathetic neurons, but GFRalpha1 immunofluorescence was unaffected in these neurons. CONCLUSION: These studies show that there are profound changes within the pelvic ganglion after penile nerve injury. Sprouting of injured postganglionic axons occurs concurrently with structural or chemical changes in preganglionic terminals. New growth of postganglionic axon collaterals within the ganglion raises the possibility of the formation of aberrant synaptic connections between injured and un-injured ganglion neurons. Together these changes demonstrate a broader effect on the pelvic autonomic circuitry than simply loss of neuroeffector connections. These structural changes are accompanied by potential changes in neurotrophic factor signalling due to altered expression of receptors for members of the GDNF family. Together our results advance understanding of the responses of pelvic autonomic nerve circuits to injury and may assist in designing strategies for promoting regeneration.
The effects of stress on splenic immune function are mediated by the splenic nerve.
Intermittent footshock (FS) suppresses immune function of spleen cells. To determine if the autonomic nervous system mediates this immunosuppression in spleen cells, we tested whether cutting the splenic nerve, which depletes splenic norepinephrine levels by 98-100% and eliminates catecholamine fibers, blocks the effects of stress. Splenic nerve sections, sham operations, or no surgery were performed on male Sprague-Dawley rats. Ten days later, rats were injected with sheep red blood cells (SRBC). Three days later, rats were placed in a chamber equipped with a shock grid. Foot shock (1.6 mA) was administered for 5 s on a VI 3.5 min schedule for 60 min. Each FS was preceded by a 15-s warning tone. Controls were treated identically except for the FS. The next day spleen cells were harvested and the number of IgM plaque-forming cells (PFCs) determined. For the sham and unoperated control animals, the number of PFCs was reduced for the stressed animals relative to the nonstressed controls, and there was no effect of the sham surgeries. In contrast, there was no difference between the stressed and nonstressed groups in which the splenic nerve had been sectioned, and their PFC response was comparable to the controls. Next we examined the effects of FS on the proliferative response to mitogens (PHA and ConA) following splenic nerve sections or sham operations. One week following surgery, animals were given a 60-min session of FS or exposed to the chamber/tone without FS. Rats were then killed, spleens harvested, and the proliferative response to mitogens determined.(ABSTRACT TRUNCATED AT 250 WORDS)
Behavioral task-induced bronchodilation in asthma during active and passive tasks: a possible cholinergic link to psychologically induced airway changes.
This study investigated pulmonary and autonomic reactions to active and passive behavioral laboratory tasks among asthmatic subjects. It also examined the relationship between airway irritability, as measured by the methacholine challenge test (MCT), and autonomic activity and reactivity to these tasks. Fifty-one asthmatic and 37 nonasthmatic subjects were exposed to psychological laboratory tasks involving either active (mental arithmetic and reaction time) or passive (films depicting shop accidents and thoracic surgery) response. The MCT was given to asthmatics in a separate session. Active tasks reduced respiratory impedance, as measured by forced oscillation pneumography. They also increased heart rate and appeared to block vagal activity, as measured by respiratory sinus arrhythmia (RSA). Airway irritability as assessed by the MCT was positively related to amplitude of RSA and to skin conductance levels. Our data suggest that active and passive behavioral tasks may produce different pulmonary effects among both asthmatic and nonasthmatic individuals. Engaging in tasks requiring active responses may produce temporary improvements in pulmonary function. No autonomic differences were obtained between asthmatics and nonasthmatics in physiological response to stress, but greater cholinergic receptor sensitivity was suggested among high responders to methacholine.
[Surgery of hyperthyroidism: introduction (author's transl)].
Of the patients operated upon for goiter (n = 1891) within the last 10 years, 625 had hyperthyroidism. Exophthalmia was present in 22.7% toxic nodular goiter in 26.5%; the remaining patients had autonomous adenoma. The different prognosis and treatment of Graves' disease in contrast to other kinds of hyperthyroidism is discussed. The importance of radioimmunoassays and scintigraphic methods as a basis of differentiated and functional surgical treatment is emphasized. Close cooperation among all medical branches involved in the treatment of goiter is recommended.
Neurophysiological basis of sympathetic nerve-preserving surgery for lower rectal cancer--a canine model.
BACKGROUND/AIMS: The relative contribution and interrelated compensation of sympathetic signals among sympathetic components in pelvic plexus remain undefined. This study was designed to investigate the genitourinary function in response to autonomic nerve preservation and severance using a canine model. METHODOLOGY: Eighteen mongrel dogs were randomly divided into 3 groups which received severance of the hypogastric nerves on either the right side, left side, or on both sides. The hypogastric nerves and sacral sympathetic trunks were electrically stimulated and the contraction pressure of the internal urethral orifice was measured immediately, at 1- and 3-month intervals. The ejaculation function and the length of time required to reach sexual orgasm were evaluated by manual penis-stimulation. RESULTS: The difference between the left and right sides of the normal hypogastric nerve in contribution to sympathetic signals was insignificant. Compared with the hypogastric nerve, the bilateral sacral sympathetic trunks were functionally trivial in controlling the closure of the internal urethral orifice. The preserved side of the hypogastric nerve compensated for the loss of sympathetic signals of the severed side within 1 month and, thereafter, remained stationary. In contrast, the functional compensation of bilateral sacral sympathetic trunks for the severed bilateral hypogastric nerves was insignificant. When the hypogastric nerve was preserved in one or both sides, all dogs maintained normal antegrade ejaculation. If bilateral hypogastric nerves were severed, 50.0% (3/6) of the dogs lost both emission and ejaculation function; 33.3% (2/6) presented with retrograde ejaculation; and, 16.7% (1/6) presented with combined retrograde ejaculation and reduced antegrade ejaculation. The time required to reach sexual orgasm was not affected by the severance of the hypogastric nerve. CONCLUSIONS: The normal genitourinary function could be maintained only when at least one side of the hypogastric nerve was preserved.
[Altered heart rate variability but preserved temporal relationship with sleep stages in a patient with primary aldosteronism].
OBJECTIVE: In a previous study, we found oscillations in the autonomic nervous system activity--as estimated by spectral analysis of R-R intervals--strongly linked to the non-rapid-eye movement (NREM)--REM sleep cycles, with low sympathetic activity during NREM sleep and predominant sympathetic activity during REM sleep. In the present study we established the 5-min nighttime profiles in various measures of heart rate variability (HRV) in one patient with primary aldosteronism before and after successful surgery of Conn adenoma. METHODS: One patient (female, 36 years old) with primary aldosteronism underwent two experimental nights a few weeks before and after surgery by coeliscopy in which sleep and cardiac recordings were made. Power spectral analysis was performed on ectopic-free R-R intervals with a fast Fourier transform. We calculated also the standard deviation of normal R-R intervals (SDNN) and the root mean square difference among successive R-R intervals (RMSSD). RESULTS: While removal of adenoma resulted in a rapid complete normalization of blood pressure and classical signs and biological symptoms of aldosterone hypersecretion, HRV profile did not changed a few weeks after surgery. The overnight SDNN was low although not abnormal at 38 and 33 ms before and after surgery respectively vs 58 +/- 15 ms (33 to 83) in normal female controls. RMSSD was low although not abnormal at 33 and 31 ms before and after surgery respectively vs 60 +/- 20 ms (20 to 105). The total spectrum power was low although not abnormal at 2.3 and 1.8 ms2 before and after surgery, respectively vs 3.2 +/- 1.1 ms2 (1.4 to 4.9). One out of the 8 controls had comparable or lower SDNN (33 ms), RMSSD (20 ms) and total power (1.4 ms2) values. While LF/HF ratio was comparable, the VLF (0.003-0.04 Hz) and LF (0.04-0.15 Hz) relative power were decreased and increased respectively in the patient compared in controls. Despite this reduced HRV, the normal temporal relationship of spectral parameters with specific sleep stages was preserved. CONCLUSION: Altered HRV with normal temporal relationships with specific sleep stages was observed in a patient with primary hyperaldosteronism. This HRV profile did not changed 20 weeks after successful surgery i.e. complete remission of classical signs and symptoms of aldosterone hypersecretion.
Spontaneous baroreflex cardiac sensitivity in end-stage liver disease: effect of liver transplantation.
BACKGROUND AND OBJECTIVE: End-stage liver disease is associated with an imbalance in the autonomic nervous system. The purpose of this study was to estimate the effect of liver transplantation on this imbalance. METHOD: The study involved 10 patients undergoing liver transplantation and 9 patients without liver impairment undergoing liver surgery. The spontaneous baroreflex sensitivity was measured before and 1 month after surgery for the liver surgery group; before and 1, 3, 6, 12 and 18 months after orthotopic liver transplantation. RESULTS: The spontaneous baroreflex slope of patients with end-stage liver disease was decreased before liver transplantation compared to the liver surgery group (3.9 +/- 2.5 ms mmHg(-1) vs. 9.9 +/- 5.0 ms mmHg(-1), P = 0.002). The mean slope was significantly increased at 12 and 18 months compared to the pre-transplantation value (3.9 +/- 2.5 ms mmHg(-1) vs. 8.1 +/- 6.6 ms mmHg(-1) and 7.4 +/- 4.8 ms mmHg(-1), respectively; P = 0.042). Nevertheless, further analysis of individual data showed that only four patients exhibited a marked increase in their baroreflex slope 12 months after the liver transplantation whereas it remained decreased in the six others. CONCLUSIONS: These results confirm that the baroreflex sensitivity is depressed in end-stage liver disease in line with an autonomic nervous system imbalance. The liver transplantation reverses this disturbance only in some patients.
The surgical anatomy of the rectum--a review with particular relevance to the hazards of rectal mobilisation.
The major complications of rectal surgery that are wholly or partially avoidable by the use of an anatomically based dissection are haemorrhage from presacral veins, perforation of the rectum, damage to pelvic autonomic nerves and inadequate clearance of a rectal cancer. Important technical points in minimising the incidence of these complications are: (1) posterior dissection in the presacral space; (2) entry to this space by sharp dissection immediately posterior to the superior rectal artery; (3) deliberate incision of the rectosacral fascia; (4) anterior dissection posterior to Denonvilliers fascia in benign disease; (5) removal of the entire mesorectum for low rectal cancer. Other anatomical points not widely appreciated are: 1. The middle rectal artery does not run in the lateral ligaments of the rectum, but below them, on levator ani. It reaches the rectum by penetrating Denonvilliers' fascia. 2. The lateral ligaments may contain an accessory middle rectal artery in 25% of cases. 3. The pelvic autonomic nerves are buried in endopelvic fascia on the pelvic side wall, but come to lie close to the anterior aspect of the rectum at the level of the prostate or upper vagina.
Nerve-sparing surgery with lateral node dissection for advanced lower rectal cancer.
133 patients who underwent nerve-sparing surgery with lateral dissection for lower rectal cancer were analysed for survival and functional results, operative burdens, and modes of recurrence. In 84% of patients an acceptable urinary function was preserved. Operative time averaged 334 min, and blood loss averaged 935 ml. The 5-year survival rate was 67% in all patients, and 88% for Dukes' A, 74% for Dukes' B and 59% for Dukes' C. According to the number of positive nodes, the 5-year survival rate comprised 83% of patients with up to three nodes, and 34% of those with more than four nodes. Local recurrent rates were 2.7% in patients with Dukes' B and 13% with Dukes' C. At present, pelvic nerve-sparing procedures with lateral dissection is the most promising surgery, guaranteeing both adequate lymphadenectomy and preservation of urinary function.
Outcomes of early surgical management versus late or no surgical intervention after acute spinal cord injury.
OBJECTIVE: To compare neurologic, medical, and functional outcomes of patients with acute spinal cord injury (SCI) undergoing early (<24 h and 24-72 h) and late (>72 h) surgical spine intervention versus those treated nonsurgically. DESIGN: Retrospective case series comparing outcomes by surgical and nonsurgical groups during acute care, rehabilitation, and at 1-year follow-up. SETTING: Multicenter National Spinal Cord Injury Database. PARTICIPANTS: Consecutive patients with acute, nonpenetrating, traumatic SCI from 1995 to 2000, admitted in the first 24 hours after injury. Surgical spinal intervention was likely secondary to nature of injury and the need for spinal stabilization. Interventions Not applicable. MAIN OUTCOME MEASURES: Changes in neurologic outcomes (motor and sensory levels, motor index score, American Spinal Injury Association [ASIA] Impairment Scale [AIS]), medical complications (pneumonia and atelectasis, deep vein thrombosis and pulmonary embolism, pressure ulcers, autonomic dysreflexia, rehospitalization), and functional outcomes (acute and rehabilitation length of stay [LOS], hospital charges, FIM instrument score, FIM motor efficiency scores). RESULTS: Subjects in the early surgery group were more likely ( P <.05) to be women, have paraplegia, and have SCI caused by motor vehicle collisions. The nonsurgical group was more likely ( P <.05) to have an older mean age and more incomplete injuries. ASIA motor index improvements (from admission to 1-y follow-up) were more likely ( P <.05) in the nonsurgical groups, as compared with the surgical groups. Those with late surgery had significantly ( P <.05) increased acute care and total LOS and hospital charges along with higher incidence of pneumonia and atelectasis. No differences between groups were found for changes in neurologic levels, AIS grade, or FIM motor efficiency. CONCLUSIONS: ASIA motor index improvements were noted in the nonsurgery group, though likely related to increased incompleteness of injuries within this group. Early versus late spinal surgery was associated with shorter LOS and reduced pulmonary complications, however, no differences in neurologic or functional improvements were noted between early or late surgical groups.
Power spectral heart rate analysis demonstrates decreased activity of the sympathetic nervous system during low bupivacaine spinal anesthesia.
STUDY OBJECTIVE: To evaluate the onset of spinal anesthesia with power spectral heart rate analysis to determine the influence of the block on the autonomic nervous system. DESIGN: Prospective, clinical evaluation. SETTING: Tertiary-care teaching hospital. PATIENTS: 27 ASA physical status I and II patients scheduled for lower extremity orthopedic surgery and free of major cardiac disease or cardiac drugs with direct influence of heart rate (HR) or blood pressure (BP). INTERVENTIONS: Prior to anesthesia, a baseline power spectral heart rate reading was taken in the supine position. Spinal anesthesia was established in the sitting position with 15 mg of bupivacaine and 0.2 mg epinephrine introduced at the L3-L4 interspace with a 22-gauge Quincke needle. The patient was returned supine, and power spectral heart rate data were again collected at 5-minute intervals throughout the procedure. Level of the spinal block was checked at 5-minute intervals until 30 minutes and considered complete when two consecutive readings were unchanged. MEASUREMENTS AND MAIN RESULTS: Heart rate and BP were recorded at baseline and at five-minute intervals after injection. Power spectral heart rate data included low-frequency activity (LFa), high-frequency activity (HFa), and the ratio (LFa/HFa). Spinal level achieved was recorded by thoracic dermatome at complete onset. Heart rate and BP remained within 20% of control in all cases. Complete onset of the spinal block was present by 30 minutes in all cases. The average level of spinal anesthesia was T8. Compared with baseline, LFa activity decreased, HFa activity remained unchanged, and the ratio was decreased. During endoprosthesis insertion, 9 of 14 total hip patients had a transient ten-fold increase in LFa activity, without HFa change, and a corresponding increase in the ratio. CONCLUSIONS: Power spectral heart rate analysis during low thoracic bupivacaine spinal anesthesia is compatible with decreased sympathetic activity during stable hemodynamic intervals. Insertion of hip endoprosthesis resulted in a dramatic, transient increase in sympathetic activity, indicating that sympathetic activation was still possible despite the presence of surgical anesthesia from the subarachnoid block.
Palmar hyperhidrosis CT guided chemical percutaneous thoracic sympathectomy.
Palmar hyperhidrosis or excessive sweating of the hands causes, to those affected, emotional and physical disturbance and impediment in professional and social life. The cause is unknown. Sweat glands are innervated by the sympathetic chain of the autonomous nervous system. The center of sympathetic regulation of the upper extremities is located between the segments of D.2-D.9 of the spinal cord. Accepted treatment consists of surgery aimed to excise the third thoracic sympathetic ganglion. Besides the surgical procedure as such, and its complications, there are complications inherent to the excision of the ganglion. These are Horner's syndrome, compensatory sweating in other parts of the body, and recurrence of sweating. CT guided chemical percutaneous thoracic sympathectomy presents an alternative, which in the event of failure does not prevent ensuing surgery. The preliminary experience with this procedure in 50 patients is presented and discussed.
Pain relief and functional recovery after endoscopic interventions for chronic pancreatitis.
BACKGROUND: Pain and functional deterioration in chronic pancreatitis is multifactorial. Early surgery in non-alcoholic patients with mild to moderate chronic pancreatitis can relieve pain and prevent progression of pancreatic insufficiency for some time, but the good results are only short term. Endoscopic intervention can relieve pain and recover pancreatic function without surgery. METHODS AND RESULTS: To achieve the burned out state of chronic pancreatitis, occlusion of the pancreatic duct was first attempted by our team with Ethibloc at ERCP. Temporary obstruction of the pancreatic duct did not result in a long-lasting symptom and relapse-free situation because of early recovery of pancreatic function. On the contrary, endoscopic simple and double papillotomy, pancreatic drainage with citrate lavage, biliary endoprosthesis with multiple stents and endoscopic decompression of pseudocysts with or without jejunal feeding resulted in pain-free patients for a considerable time and in several cases significant functional recovery occurred. In cases where pain remained, percutaneous celiac plexus block with long-lasting steroids can be applied and only if all of these treatments fail should surgery be recommended. CONCLUSION: Endoscopic intervention can successfully substitute for surgery for chronic pancreatitis in individual cases.