Stricture rate after chemoradiotherapy and radiotherapy for oesophageal squamous cell carcinoma: a 20-year experience.

BACKGROUND: Definitive chemoradiation for oesophageal squamous cell carcinoma (SCC) is the first-line treatment in many centres. However, it is not without morbidity. We assess outcomes for patients treated with definitive chemoradiotherapy and radiotherapy. METHODS: A retrospective review of a prospectively maintained database (Radiotherapy Department, Canterbury District Health Board) was undertaken. All patients who underwent definitive radiotherapy for oesophageal SCC between October 1996 and April 2015 were included. RESULTS: Sixty patients underwent chemoradiotherapy with curative intent and 17 underwent definitive radiotherapy with curative intent. Median age was 69 years (44-84 years) for those undergoing chemoradiotherapy and 73 years (36-85 years) for those who underwent definitive radiotherapy. Tumour location in all patients was upper third in 14 (18%), middle third in 39 (51%), lower third in 22 (29%) cases and junctional tumour in two (3%). Staging information was complete for 73 of 77 patients (stage I 16/77 (21%), stage II 40/77 (52%), stage III 17/77 (22%)). Median dose of external beam radiotherapy for those who underwent definitive chemotherapy was 50.4 Gy (30-63 Gy) and 60 Gy (50-64 Gy) for definitive radiotherapy. Median length of follow-up was 39 months (range 4-120 months). Strictures developed in 58% of all patients (52% chemoradiotherapy and 76% definitive radiotherapy). Twenty-four (32%) patients were dilated and 14 (18%) stented. The chemoradiotherapy group had higher 5-year survival than definitive radiotherapy group (34% versus 6%, P = 0.0034). CONCLUSION: Oesophageal SCC treated with chemoradiation has a 5-year survival rate of 34%. Post-treatment strictures occur in 52% of patients with chemoradiotherapy and 76% with definitive radiotherapy.

The Pattern of Adjustments after Laparoscopic Adjustable Gastric Band.

BACKGROUND: The success of laparoscopic adjustable gastric band (LAGB) is dependent on gradual adjustments over time. The aim of this study is to describe that pattern of LAGB adjustments that are required after surgery. METHODS: A non-randomized observational study of consecutive LAGB from a single practise. Patients were sourced from a prospective database. Details of each LAGB adjustment were recorded along with weight loss and complications. RESULTS: There were 125 consecutive LAGB between March 2009 and September 2011 (mean age 46.6 ± 11.9 years; 113 female, BMI 42.1 ± 5.9 kg/m(2)). The mean %EBWL was 41.4 ± 19.1 % at 2 years. There was a total of 746 band adjustments with mean 7.1 ± 4.4 per patient. Approximately, a third of patients (34 %) reached optimal volume within 6 months but 49 patients (39 %) still required adjustments beyond a year. Weight loss was maximal prior to the first adjustment (41 % of mean total weight loss). The rate of weight loss decreased down to 1-3 %EBWL between later fills despite repeated increases in band volume. Urgent deflations were required in 63 patients with 24 of these patients having multiple overfills. There were two patients who had gastric prolapse but no other LAGB-related complications occurred in the first 2 years after surgery. CONCLUSIONS: LAGB requires a considerable postoperative commitment that may take several months. Overfills are common and may be the result of a false perception that tightening the band will hasten weight loss.

Establishing a reproducible large animal survival model of laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: The advent of metabolic surgery and the increasing focus on the substantial resolution rate of type 2 diabetes after laparoscopic Roux-en-Y gastric bypass (LRYGB) call for additional fundamental investigations as to the mechanisms behind this effect. These investigations require an adequate animal model. Our objective was to develop a reproducible survival model of LRYGB performed in a large animal at a tertiary university hospital. METHODS: LRYGB was performed on 11 Yorkshire pigs that where then followed for 6 weeks. The operative time, morbidity, and mortality were recorded for each case. Necropsy was performed, and the anastomoses were harvested and inspected for leaks. RESULTS: The surgical technique and difficulties are carefully described. Of the 11 pigs, 10 survived to the end of the study period. The 1 death was from intraoperative cardiac dysrhythmia. The postoperative complications consisted of a postoperative febrile episode in 2 pigs. The mean initial weight was 31.5 ± 3.4 kg. The mean operative time was 214 ± 71 minutes. No anastomotic leaks were identified at necropsy or on histologic examination of anastomoses. The mean weight gain at the end of the study period was .8 ± 1.4 kg compared with an expected 17.5 kg weight gain. CONCLUSION: We have described an effective survival porcine model of LRYGB that can be consistently reproduced. This will enable additional investigation into the complex physiologic mechanisms that control hunger, weight loss, and the development, as well as resolution, of type 2 diabetes, potentially leading to the development of novel, targeted bariatric procedures and diabetic treatments.

Acute pancreatitis severity is exacerbated by intestinal ischemia-reperfusion conditioned mesenteric lymph.

OBJECTIVE: To determine the effect of intestinal ischemia-reperfusion (IIR) on acute pancreatitis (AP) and the role of mesenteric lymph. SUMMARY BACKGROUND DATA: Intestinal ischemia is an early feature of AP and is related to the severity of disease. It is not known whether this contributes to the severity of AP or is a consequence. METHODS: Two experiments are reported here using intravital microscopy and a rodent model of mild acute pancreatitis (intraductal 2.5% sodium taurocholate). In the first, rats had an episode of IIR during AP that was produced by temporary occlusion of the superior mesenteric artery (30 min or 3 x 10 min) followed by 2h reperfusion. In a second study rats with AP had an intravenous infusion of mesenteric lymph collected from donor rats that had been subjected to IIR. In both experiments the pancreatic erythrocyte velocity (EV), functional capillary density (FCD), leukocyte adherence (LA), histology and edema index were measured. RESULTS: The addition of IIR to AP caused a decline in the pancreatic microcirculation greater than that of AP alone (EV 42% of baseline vs. 73% of baseline AP alone, FCD 43% vs 72%, LA 7 fold increase vs 4 fold increase). This caused an increased severity of AP as evidenced by 1.4-1.8 fold increase of pancreatic edema index and histologic injury respectively. A very similar exacerbation of microvascular failure and increased pancreatitis severity was then demonstrated by the intravenous infusion of IIR conditioned mesenteric lymph from donor animals. CONCLUSIONS: Unidentified factors released into the mesenteric lymph following IIR injury are capable of exacerbating AP. This highlights an important role for the intestine in the pathophysiology of AP pathogenesis and identifies mesenteric lymph as a potential therapeutic target.

Probing the urinary proteome of severe acute pancreatitis.

BACKGROUND: Proteinuria is a characteristic feature of severe acute pancreatitis (SAP) that may allow unique insights into AP pathophysiology. This study used a proteomic approach to differentiate the abundant urinary proteins in AP patients. MATERIALS AND METHODS: Urine samples were prospectively collected from 4 groups (5 SAP, 10 mild gallstone AP, 7 mild alcohol AP, 7 controls). Reverse-phase high-performance liquid chromatography (RP-HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (LC MALDI) were used to identify urinary proteins and determine any differences between the groups. RESULTS: There were 17 RP-HPLC major peaks in SAP groups of significantly greater absorbance magnitude than the corresponding ones in mild and control groups. Various mass spectrometry methods were used to identify 21 different parent proteins from these SAP peaks. They included fibrinogen, serum amyloid A, insulin and calcitonin gene-related peptides. There were no identifiable protein peaks at the corresponding elution times in the mild pancreatitis and controls samples. DISCUSSION: Proteomic techniques offer a unique unexplored window into AP pathophysiology. The utility of these proteins as markers of pancreatitis severity now need to be further investigated and the identification extended to the full urinary proteome as technology permits.

Primary hyperparathyroidism: referral patterns and outcomes of surgery.

BACKGROUND: Parathyroidectomy has long been established as an effective treatment for primary hyperparathyroidism (HPT). METHODS: A 15-year retrospective audit was made by surgeons at North Shore Hospital, Auckland, of 33 patients with primary HPT who had parathyroidectomy. RESULTS: There were 22 females and 11 males, ranging in age from 18 to 77 years (median 63 years). Initial diagnosis was predominantly by a general practitioner (72%), who invariably referred to a physician. Referral to surgery was made by general physicians (55%), endocrinologists (33%) and geriatricians (6%). Delay between diagnosis and referral for surgery ranged from 8 days to 10 years (median 7 months), and exceeded 2 years in 24% of patients. Twenty-eight (85%) were symptomatic: 13 (39%) had renal symptoms, 13 (39%) had bone disease, 10 (31%) had gastrointestinal complaints, seven (21%) had psychiatric illnesses and six (18%) had fatigue. The high incidence of symptoms was matched by high biochemical values (mean serum calcium level 2.97 mmol/L), and large parathyroid glands (mean weight 2001 mg). Twenty-nine patients (88%) had single adenomas, two (6%) had chief cell hyperplasia and two (6%) had carcinoma. Thirty-one (94%) were cured of their primary HPT. CONCLUSIONS: Parathyroidectomy is a safe and effective treatment for primary HPT but depends upon referral from non-surgical clinicians. A large proportion of patients have long delays before their surgery, and the group selected for surgery is referred with severe disease.