Long-term outcome of kidney transplant by using restored kidney grafts after tumour ex vivo excision - a prospective study.

The aim of this study is to report long-term outcomes of kidney transplantation by using the kidney graft after a small tumour ex vivo excision. A structured programme was established to use the restored kidney graft from urological referral after radical nephrectomy. The criteria were defined as tumour size ≤3 cm, margin clear on frozen section and recipients aged ≥60 years or those on the urgent list for transplantation as a result of imminent lack of dialysis access. The recipients were followed up regularly for surveillance of tumour recurrence. Between February 2007 and February 2018, 28 recipients had kidney transplantation by using the restored kidney grafts. The tumour size was 2.6 ± 0.7 cm. The follow-up was median 7 years without evidence of tumour recurrence. The patient and graft survival was satisfactory. Kidney transplantation by using restored kidneys after a small tumour excision is a novel source for selected recipients. The long-term patient and graft survival is satisfactory. Although there is a risk of tumour recurrence, it is rare event. Together with literature review, we would support use of kidney graft after a small tumour excision for selected recipients.

Iron-induced oxidative rat liver injury after non-heart-beating warm ischemia is mediated by tumor necrosis factor α and prevented by deferoxamine.

This study investigated iron-induced injury after warm ischemia in a non-heart-beating (NHB) rat liver model and the effects of deferoxamine (DFO). Livers from heart-beating (HB) rats or rats that were NHB for 60 minutes were stored in University of Wisconsin solution for 5 hours at 4°C [cold storage (CS)] and then were subjected to 2 hours of machine reperfusion (MRP) at 37°C. Three NHB groups were compared: (1) no DFO, (2) DFO 30 minutes before cardiac arrest and during CS and MRP, and (3) DFO during CS and MRP. Aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels in the NHB perfusate were significantly elevated (P < 0.01) in comparison with levels in HB controls after CS and MRP. After CS, the levels of iron and tumor necrosis factor α (TNF-α) were 0.077 ± 0.007 µmol/g and 151 ± 26 pg/g, respectively, in the NHB group and 0.022 ± 0.004 µmol/g and 17 ± 7 pg/g, respectively, in the HB group (P < 0.01). After MRP, LDH significantly correlated with iron (R(2) = 0.81, P < 0.01). The DFO pretreatment of NHB donors decreased AST (7.3 ± 0.8 versus 4.0 ± 0.5 U/g of liver, P < 0.05) and LDH (42.5 ± 4.1 versus 20.4 ± 2.5 U/g of liver, P < 0.05) with 2 hours of MRP and increased bile flow during MRP (142 ± 34 versus 240 ± 18 µL/g, P < 0.05). It also reduced the levels of iron (0.077 ± 0.007 versus 0.050 ± 0.008 µmol/g, P < 0.05) and TNF-α (151 ± 26 versus 51 ± 13 pg/g, P < 0.05) after CS and the levels of lipid peroxidation products F2-isoprostane (149 ± 11 versus 99 ± 10 ng/g, P < 0.05) and malondialdehyde (1.58 ± 0.1 versus 1.14 ± 0.08 µmol/g, P < 0.05) after MRP. In conclusion, iron-initiated oxidative stress is likely involved in NHB donor liver injury, and importantly, DFO pretreatment reduces liver damage.

Laparoscopic surgery for orthotopic kidney transplant in the pig model.

BACKGROUND: Laparoscopic surgery has become the preferred approach in surgical practice due to multiple benefits. Over the last decade, kidney transplant by laparoscopic or robotic techniques have been explored. The aim of this study is to establish a new laparoscopic technique for kidney orthotopic transplant. MATERIALS AND METHODS: The study was approved by the Animal Ethics Committee of the University. Ten live female pigs (Sus scrofa), weighing 45-50 kg, underwent laparoscopic kidney orthotopic transplant on left side under general anesthesia, and the opposite right kidney was defunctioned by complete ligation of the ureter at the same time. RESULTS: The vital signs of all pigs were stable during the surgery and postoperative period. There were no intraoperative complications and no conversion to open surgery. The laparoscopic kidney transplant was successful in seven of 10 pigs. Seven pigs were observed up to 4 wk as planned in the study. DISCUSSION: To our knowledge, this is the first study of laparoscopic kidney orthotopic transplant in pig model with satisfactory immediate graft function. It was demonstrated that laparoscopic kidney transplant is a feasible, reliable, and safe procedure. However, it is a very demanding technique. Adequate training is mandatory for performing laparoscopic kidney transplant. This study could be used as a training model for surgeons who wish to perform human laparoscopic kidney transplant in the future.

Laparoscopic surgery for kidney orthotopic transplant in the pig model.

BACKGROUND AND OBJECTIVES: Laparoscopic surgery has rapidly expanded in surgical practice with well-accepted benefits of minimal incision, less analgesia, better cosmetics, and quick recovery. The surgical technique for kidney transplantation has remained unchanged since the first successful kidney transplant in the 1950s. Over the past decade, there were only a few case reports of kidney transplantation by laparoscopic or robotic surgery. Therefore, the aim of this study is to develop a laparoscopic technique for kidney transplantation at the region of the native kidney. METHODS: After initial development of the laparoscopic technique for kidney transplant in cadaveric pigs, 5 live pigs (Sus scrofa, weighing 45-50 kg) underwent laparoscopic kidney transplant under general anesthesia. First, laparoscopic donor nephrectomy was performed, and then the kidney was perfused and preserved with cold Ross solution. The orthotopic auto-transplant was subsequently performed using the laparoscopic technique. The blood flow of the kidney graft was assessed using Doppler ultrasonography, and urine output was monitored. RESULTS: The laparoscopic kidney transplant was successful in 4 live pigs. Immediate urine output was observed in 3 pigs. The blood flow in the kidney was adequate, as determined using Doppler ultrasonography. CONCLUSION: It has been shown that laparoscopic kidney orthotopic transplant is feasible and safe in the pig model. Immediate kidney graft function can be achieved. A further study will be considered to identify the potential surgical morbidity and mortality after recovery in a pig model before translating the technique to clinical human kidney transplantation.

Resection of previously inoperable retroperitoneal liposarcoma.

We present a case of successful resection of a large right upper quadrant retroperitoneal dedifferentiated liposarcoma involving multiple adjacent organs, initially considered inoperable in a patient in his 40s. This case highlights the importance of extensive preoperative planning and a multidisciplinary approach in achieving a greater chance of curative resection. Preoperative optimisation included neoadjuvant chemotherapy, concurrent portal vein embolisation and hepatic vein embolisation. The patient then underwent en-bloc resection, including total pancreatectomy, hemihepatectomy and vena caval resection in conjunction with extracorporeal membrane oxygenation and percutaneous venovenous bypass.

Subset-specific Retention of Donor Myeloid Cells After Major Histocompatibility Complex-matched and Mismatched Liver Transplantation.

BACKGROUND: During solid organ transplantation, donor leukocytes, including myeloid cells, are transferred within the organ to the recipient. Both tolerogenic and alloreactive roles have been attributed to donor myeloid cells; however, their subset-specific retention posttransplantation has not been investigated in detail. METHODS: Major histocompatibility complex (MHC)-matched and mismatched liver transplants were performed in mice, and the fate of donor and recipient myeloid cells was assessed. RESULTS: Following MHC-matched transplantation, a proportion of donor myeloid cells was retained in the graft, whereas others egressed and persisted in the blood, spleen, and bone marrow but not the lymph nodes. In contrast, after MHC-mismatched transplantation, all donor myeloid cells, except Kupffer cells, were depleted. This depletion was caused by recipient T and B cells because all donor myeloid subsets were retained in MHC-mismatched grafts when recipients lacked T and B cells. Recipient myeloid cells rapidly infiltrated MHC-matched and, to a greater extent, MHC-mismatched liver grafts. MHC-mismatched grafts underwent a transient rejection episode on day 7, coinciding with a transition in macrophages to a regulatory phenotype, after which rejection resolved. CONCLUSIONS: Phenotypic and kinetic differences in the myeloid cell responses between MHC-matched and mismatched grafts were identified. A detailed understanding of the dynamics of immune responses to transplantation is critical to improving graft outcomes.

Liver Transplant for Adult Recurrent Hepatic Mesenchymal Hamartoma and a Feasible Treatment Modality: A Case Report and Literature Review.

BACKGROUND: Adult hepatic mesenchymal hamartoma (HMH) is an extremely rare hepatic tumor. Recurrence following complete resection is uncommon. Liver transplantation (LT) is described as a possible treatment option in nonresectable HMH. We conducted a systematic review investigating LT in adult HMH followed by a case report describing evidence of extensive recurrence following complete resection of large right-sided HMH requiring LT. CASE REPORT: A 46-year-old woman with symptomatic large right-hepatic HMH underwent right hemi-hepatectomy with histologic evidence of complete resection. Two and a half years postresection, she presented with abdominal pain and distension; imaging revealed large multi-septated hepatic cystic lesions within the liver suggestive of extensive recurrence of disease with concerns of malignant sarcomatous transformation. After a multidisciplinary team discussion, the lesion was deemed unresectable and the patient was referred for LT. Findings on transplantation included giant multiple hepatic cystic lesions occupying the entire abdomen and histopathological analysis confirmed recurrent HMH with no malignancy. The 6-month follow-up was unremarkable with no signs of postoperative complications or rejection. CONCLUSION: We identified only 3 reported adult unresectable HMH cases in the English literature requiring LT, with good clinical outcome and no rejection on a 1-year follow-up. To our knowledge, we report the first recurrent HMH that required LT in the English literature. Current evidence suggests possible malignant sarcomatous transformation of those lesions. No guidelines exist on postresection surveillance for HMH; however, given their malignant potential, we suggest a benefit of imaging-based surveillance following HMH resection. Offering LT for nonresectable or recurrent HMH is a feasible treatment modality with a reported good outcome.

Late-onset carbamoyl phosphate synthetase 1 deficiency in an adult cured by liver transplantation.

Urea cycle disorders (UCDs) are rare causes of hyperammonemic encephalopathy in adults. Most UCDs present in childhood and, if unrecognized, are rapidly fatal. Affected individuals who survive to adulthood may remain undiagnosed because of clinicians' unawareness of the condition or atypical presentations. We describe the case of a 49-year-old man who initially presented with a stroke and developed hyperammonemic encephalopathy over a period of 8 months. A diagnosis of carbamoyl phosphate synthetase type 1 deficiency was made, and the patient was referred for liver transplantation. One year after liver transplantation, the patient had normal plasma ammonia concentrations and had returned to work.

Dynamic changes to tissue-resident immunity after MHC-matched and MHC-mismatched solid organ transplantation.

The heterogeneous pool of tissue-resident lymphocytes in solid organs mediates infection responses and supports tissue integrity and repair. Their vital functions in normal physiology suggest an important role in solid organ transplantation; however, their detailed examination in this context has not been performed. Here, we report the fate of multiple lymphocyte subsets, including T, B, and innate lymphoid cells, after murine liver and heart transplantation. In major histocompatibility complex (MHC)-matched transplantation, donor lymphocytes are retained in liver grafts and peripheral lymphoid organs of heart and liver transplant recipients. In MHC-mismatched transplantation, increased infiltration of the graft by recipient cells and depletion of donor lymphocytes occur, which can be prevented by removal of recipient T and B cells. Recipient lymphocytes fail to recreate the native organs' phenotypically diverse tissue-resident lymphocyte composition, even in MHC-matched models. These post-transplant changes may leave grafts vulnerable to infection and impair long-term graft function.

Excellent Contemporary Graft Survival for Adult Liver Retransplantation: An Australian and New Zealand Registry Analysis From 1986 to 2017.

BACKGROUND: Liver retransplantation is technically challenging, and historical outcomes are significantly worse than for first transplantations. This study aimed to assess graft and patient survival in all Australian and New Zealand liver transplantation units. METHODS: A retrospective cohort analysis was performed using data from the Australia and New Zealand Liver Transplant Registry. Graft and patient survival were analyzed according to era. Cox regression was used to determine recipient, donor, or intraoperative variables associated with outcomes. RESULTS: Between 1986 and 2017, Australia and New Zealand performed 4514 adult liver transplants, 302 (6.7%) of which were retransplantations (278 with 2, 22 with 3, 2 with 4). The main causes of graft failure were hepatic artery or portal vein thrombosis (29%), disease recurrence (21%), and graft nonfunction (15%). Patients retransplanted after 2000 had a graft survival of 85% at 1 year, 75% at 5 years, and 64% at 10 years. Patient survival was 89%, 81%, and 74%, respectively. This was higher than retransplantations before 2000 (P < 0.001). Univariate analysis found that increased recipient age (P = 0.001), recipient weight (P = 0.019), and donor age (P = 0.011) were associated with decreased graft survival prior to 2000; however, only increased patient weight was significant after 2000 (P = 0.041). Multivariate analysis found only increased recipient weight (P = 0.042) and donor age (P = 0.025) was significant prior to 2000. There was no difference in survival for second and third retransplants or comparing time to retransplant. CONCLUSIONS: Australia and New Zealand have excellent survival following liver retransplantation. These contemporary results should be utilized for transplant waitlist methods.

Selective internal radiation therapy (SIRT) with yttrium-90 microspheres for unresectable intrahepatic cholangiocarcinoma.

Unresectableintrahepaticcholangiocarcinoma has a very poor prognosis despite various treatment options. The case presented describes the diagnostic challenges of a young pregnant woman with unresectable cholangiocarcinoma. The current treatment options for cholangiocarcinoma have limited evidence and high recurrence rate. Given the young age of this patient, selective internal radiotherapy was trialled with traditional chemotherapy with a clinically significant result. This case highlights the delays when diagnosing cholangiocarcinoma in younger patients and the possibility of selective internal radiation therapy in combination with chemotherapy as a potential first-line treatment for a complete response in unresectable disease.

Notch ligation by Delta1 inhibits peripheral immune responses to transplantation antigens by a CD8+ cell-dependent mechanism.

Notch signaling plays a fundamental role in determining the outcome of differentiation processes in many tissues. Notch signaling has been implicated in T versus B cell lineage commitment, thymic differentiation, and bone marrow hematopoietic precursor renewal and differentiation. Notch receptors and their ligands are also expressed on the surface of mature lymphocytes and APCs, but the effects of Notch signaling in the peripheral immune system remain poorly defined. The aim of the studies reported here was to investigate the effects of signaling through the Notch receptor using a ligand of the Delta-like family. We show that Notch ligation in the mature immune system markedly decreases responses to transplantation antigens. Constitutive expression of Delta-like 1 on alloantigen-bearing cells renders them nonimmunogenic and able to induce specific unresponsiveness to a challenge with the same alloantigen, even in the form of a cardiac allograft. These effects could be reversed by depletion of CD8+ cells at the time of transplantation. Ligation of Notch on splenic CD8+ cells results in a dramatic decrease in IFN-gamma with a concomitant enhancement of IL-10 production, suggesting that Notch signaling can alter the differentiation potential of CD8+ cells. These data implicate Notch signaling in regulation of peripheral immunity and suggest a novel approach for manipulating deleterious immune responses.

Alloantibody-associated chronic rejection of MHC class I-disparate heart grafts is modulated by intravenous soluble donor alloantigen.

Increasing evidence suggests that there may be a causal relationship between the development of donor-specific alloantibodies and chronic allograft vasculopathy (CAV). PVG.RT1(u) rat heart allografts spontaneously undergo chronic rejection when transplanted into unmodified PVG.R8 congenic recipients that differ only at the classical MHC class I RT1.A locus. Here we show that development of vasculopathy in this experimental model is associated with production of a strong anti-A(u) antibody response. Perioperative intravenous administration of recombinant soluble RT1.A(u) heavy chain that is sequence identical to donor MHC class I, or chimaeric A(u/a) (donor/recipient) protein had a variable effect resulting generally in either sensitisation and accelerated rejection, or abrogation of alloantibody and attenuation of chronic rejection. These findings highlight the potential for soluble donor MHC class I alloantigen given at the time of heart transplantation to influence alloantibody production and graft outcome.

Transjugular intrahepatic portosystemic shunt: Indications, complications, survival and its use as a bridging therapy to liver transplant in Western Australia.

INTRODUCTION: Insertion of transjugular intrahepatic portosystemic shunt (TIPS) is an established therapeutic option to treat the complications of portal hypertension. The purpose of this study is to review the experience of a single Australian institute with TIPS and evaluation of result to emphasize the indication, aetiology of portal hypertension, prognostic factors, complications and survival. Use of TIPS as a bridge to liver transplantation was also analysed. METHOD: A retrospective cohort study of patients treated with TIPS at The Western Australian Liver Transplant Unit, Sir Charles Gairdner Hospital, over a period of 12 years. Kaplan-Meier method was used for survival analysis and cox-regression analysis was used to analyse the predictors of survival. RESULTS: Fifty-three patients underwent TIPS between January 2000 and March 2012. The cumulative survival at 1 month, 1 year and 5 years was 90%, 70.9% and 43.9%, respectively. The predictors of survival were indication (variceal bleeding versus ascites, hazard ratio 3.19, CI 95%: 1.164-8.794, P = 0.024) and Model of End Stage Liver Disease score (Hazard ratio 2.513, CI 95%: 1.087-5.810, P = 0.031). Patients who underwent TIPS as a bridge to liver transplant had a 5-year survival of 71% that is comparable to the overall survival of Western Australian liver transplant unit. CONCLUSION: Transjugular intrahepatic portosystemic shunt is a safe and effective method of treatment of complications of portal hypertension. TIPS can be safely used as a bridging therapy to liver transplant. Despite small number of TIPS being performed at our institute, our technical results are comparable to the institutes with bigger number of patients.

Effect of airplane transport of donor livers on post-liver transplantation survival.

AIM: To evaluate the effect of long haul airplane transport of donor livers on post-transplant outcomes. METHODS: A retrospective cohort study of patients who received a liver transplantation was performed in Perth, Australia from 1992 to 2012. Donor and recipient characteristics information were extracted from Western Australian liver transplantation service database. Patients were followed up for a mean of six years. Patient and graft survival were evaluated and compared between patients who received a local donor liver and those who received an airplane transported donor liver. Predictors of survival were determined by univariate and multivariate analysis using cox regression. RESULTS: One hundred and ninety-three patients received a local donor liver and 93 patients received an airplane transported donor liver. Airplane transported livers had a significantly lower alanine transaminase (mean: 45 U/L vs 84 U/L, P = 0.035), higher donor risk index (mean: 1.88 vs 1.42, P < 0.001) and longer cold ischemic time (CIT) (mean: 10.1 h vs 6.4 h, P < 0.001). There was a weak correlation between CIT and transport distance (r2 = 0.29, P < 0.001). Mean follow up was six years and 93 patients had graft failure. Multivariate analysis found only airplane transport retained significance for graft loss (HR = 1.92, 95%CI: 1.16-3.17). One year graft survival was 0.88 for those with a local liver and was 0.71 for those with an airplane transported liver. One year graft loss was due to primary graft non-function or associated with preservation injury in 20.8% of recipients of an airplane transported liver compared with 4.6% in those with a local liver (P = 0.027). CONCLUSION: Airplane transport of donor livers was independently associated with reduced graft survival following liver transplantation.

Is there disparity between risk and incidence of cardiovascular disease after liver transplant?

BACKGROUND: Hypertension and hypercholesterolemia are recognized complications of liver transplantation, but whether they contribute to the development of cardiovascular disease is uncertain. We aimed first to determine the prevalence of risk factors for coronary heart disease (CHD) after liver transplantation and second to study the effect of liver transplantation on the predicted 10-year risk of developing CHD and the incidence of cardiovascular events in comparison with a matched local population. METHODS: Data on blood pressure, serum lipids, weight, diabetes mellitus, smoking, and incidence of myocardial infarction (MI) and stroke were obtained retrospectively from the case notes of 181 consecutive adult liver transplant recipients (median follow-up 54 months). The Framingham coronary risk equations were used to calculate the 10-year probability of developing CHD. RESULTS: The prevalences of hypertension and hypercholesterolemia after transplantation were 77% and 62%, respectively. The predicted 10-year risk of CHD increased from 6.9% before transplantation to 11.5% at 1 year after transplantation, whereas that of a matched local population was 7%. Compared with a matched nontransplant population, the incidence ratios for MI and stroke were 0.55 (95% confidence interval, 0.01-3.06 ) and 1.45 (95% confidence interval, 0.18-5.22), respectively. No patients died from MI or stroke. CONCLUSIONS: Liver transplant recipients have a high prevalence of risk factors for cardiovascular disease, exceeding that of the general population, and have a higher predicted risk of developing CHD. Despite this, there were no deaths from CHD or stroke during the study period.

Monitoring systemic donor lymphocyte macrochimerism to aid the diagnosis of graft-versus-host disease after liver transplantation.

BACKGROUND: The diagnosis of graft-versus-host disease (GvHD) after liver transplantation can be difficult because early symptoms are often nonspecific. In this study, the presence of donor lymphocyte macrochimerism in recipient peripheral blood was examined as a diagnostic aid for GvHD after cadaveric donor liver transplantation. METHODS: Between 1996 and 2002, 33 liver transplant recipients with a clinical suspicion of GvHD (skin rash, diarrhea, pyrexia, pancytopenia, or anemia, without an obvious alternative cause) were investigated for peripheral blood donor lymphocyte macrochimerism. Donor macrochimerism was determined at the time of first clinical presentation by a low-sensitivity polymerase chain reaction (PCR) to detect donor human leukocyte antigen (HLA) alleles using genomic DNA extracted from recipient peripheral blood. Where donor HLA alleles were detected, the percentage of donor T cells was quantified by two-color flow cytometric analysis using antibodies specific for mismatched donor and recipient HLA alleles. The relationship between the presence or absence of donor lymphocyte macrochimerism and final diagnoses based on clinical and histological criteria was examined. RESULTS: Seven of the 33 patients were PCR positive for donor HLA alleles. All had macrochimerism, with donor T lymphocyte levels ranging from 4% to 50% of circulating lymphocytes. All seven patients had normal liver function tests, skin rash, and diagnosis of GvHD histologically confirmed by skin or gut biopsies. Twenty-six patients were PCR negative, and, in 23, an alternative diagnosis was eventually established. The remaining three patients made a rapid and spontaneous recovery with no further symptoms suggestive of GvHD. CONCLUSIONS: Donor lymphocyte macrochimerism was present in all patients in whom the diagnosis of GvHD was confirmed. In patients with symptoms consistent with GvHD and a negative PCR for donor HLA, an alternative diagnosis was eventually established or the patients recovered spontaneously. Detection of donor HLA alleles in recipient peripheral blood by PCR is a useful diagnostic tool for GvHD after liver transplantation.

A human cadaver model for laparoscopic kidney transplant.

OBJECTIVES: To evaluate the technique of laparoscopic kidney transplant and demonstrate the feasibility of this procedure by an extraperitoneal approach. MATERIALS AND METHODS: The procedure was performed on 2 human cadavers. Retroperitoneal endoscopic left nephrectomy was performed. An extraperitoneal space was established by inflation of a balloon dilator. The external iliac artery and vein were exposed. A Pfannenstiel incision (6 cm) was made and a hand-access device was used. The renal artery was anastomosed to the external iliac artery (end-to-side anastomosis); the renal vein was anastomosed to the external iliac vein (end-to-side anastomosis). The ureter was anastomosed to the bladder with an extravesical tunnelling technique. RESULTS: The donor kidney grafts were obtained successfully. The preparation of the external iliac artery and vein was satisfactory. The entire procedure for the renal artery, renal vein, and ureteral anastomoses was performed with laparoscopic technique without any difficulty. CONCLUSIONS: The present model on human cadavers may provide a feasible approach for training surgeons to perform human laparoscopic kidney transplant. The present technique may be applied to clinical human kidney transplant.

Predictive value of C-reactive protein with Alvarado score in acute appendicitis.

BACKGROUND: The aim of the study was to evaluate whether C-reactive protein (CRP) level on admission could aid the diagnostic accuracy of Alvarado score in acute appendicitis. METHODS: We retrospectively evaluated hospital records and database of 234 patients (men 116, women 118, median age 28 years, range 15-87 years) who underwent appendicectomy for acute appendicitis. Patients were categorized into three groups retrospectively based on the Alvarado score. Group I: score 7-10 (n = 155), group II: score 4-6 (n = 71), group III: score less than 3 (n = 10). Negative (NPV) and positive predictive values (PPV) of CRP was calculated. RESULTS: Overall, 169 of 234 (72.2%) had histopathological confirmation of acute appendicitis. The predicted accuracy of Alvarado score was 84.5% in group I, 50.7% in group II and 25% in group III. The PPV of high CRP and NPV of normal CRP for group I was 88% and 36.4%, in group II, 63% and 72%, in group III, 33% and 86%, respectively. CONCLUSION: The Alvarado score and CRP taken together improve the predictive value of diagnosing acute appendicitis. Having a normal CRP in the equivocal group of Alvarado 4-6, should be further evaluated by advanced imaging before proceeding to appendicectomy.