Role of ablation therapy in conjunction with surgical resection for neuroendocrine tumors involving the liver.

BACKGROUND: Resection of hepatic metastasis from neuroendocrine tumors (NETs) improves quality of life and prolongs 5-year survival. Ablation can be utilized with surgery to achieve complete resection. Although several studies report long-term outcomes for patients undergoing ablation, none have explored perioperative effects of ablation in patients with metastatic NETs. AIM: To determine if intra-operative ablation during hepatectomy increases risk of adverse outcomes such as surgical site infections (SSIs), bleeding, and bile leak. METHODS: A retrospective analysis of the hepatectomy National Surgical Quality Improvement Program database from 2015-2019 was performed to determine the odds of SSIs, bile leaks, or bleeding in patients undergoing intraoperative ablation when compared to hepatectomy alone. RESULTS: Of the 966 patients included in the study, 298 (30.9%) underwent ablation during hepatectomy. There were 78 (11.7%) patients with SSIs in the hepatectomy alone group and 39 (13.1%) patients with a SSIs in the hepatectomy with ablation group. Bile leak occurred in 41 (6.2%) and 14 (4.8%) patients in the two groups, respectively; bleeding occurred in 117 (17.5%) and 33 (11.1%), respectively. After controlling for confounding variables, ablation did not increase risk of SSI (P = 0.63), bile leak (P = 0.34) or bleeding (P = 0.07) when compared to patients undergoing resection alone on multivariate analysis. CONCLUSION: Intraoperative ablation with hepatic resection for NETs is safe in the perioperative period without significant increased risk of infection, bleeding, or bile leak. Surgeons should utilize this modality when appropriate to achieve optimal disease control and outcomes.

Implementation of the Caprini risk assessment model (RAM) in surgical patients to decrease postsurgical venous thromboembolism and enoxaparin prescription at hospital discharge.

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), has been an increasingly common post-surgical complication for surgical patients. In the United States, VTE has become a leading cause of preventable hospital death with more than half occurring after discharge and are directly linked to a recent (within 30 days) hospitalization or surgery [1]. In large, hospital-associated/acquired VTE (HA-VTE) are preventable through measures such as the use of risk stratification tools and chemoprophylaxis. The project institution, a community, academic, medical center, for multiple years has consistently remained a high outlier for postoperative VTE. Also, the choice of VTE chemoprophylaxis in surgical patients at the time of discharge depended on, and varied between, the individual prescribing physician. The goal was to implement and determine the efficacy of a standardized intervention tool, the Caprini risk assessment model (RAM), for reducing postoperative VTE complications and its influence on the physician's prescription of enoxaparin at discharge. Results: Risk assessment scoring pre-operatively increased from 0% baseline to 26.3% at Plan-Do-Study-Act (PDSA) cycle 1 and demonstrated a statistically significant change (p-value = 0.006). Risk assessment scoring pre-operatively was 42.9% by PDSA cycle 2 but was not statistically significantly different from PDSA cycle 1. Risk assessment scoring post-operatively (for eligible patients) remained the same throughout all three cycles at 0%. Appropriate prescription of anticoagulation declined from baseline (12.5%) to PDSA cycle 1 (0%), and improved at PDSA cycle 2 (33.3%), however no differences were significant (p-value 0.302). The National Surgical Quality Improvement Project (NSQIP) database showed a decline in VTE occurrences at the projects institution from baseline (1.02%, 6 occurrences, 2021) to PDSA cycle 2 (0.92%, 4 occurrences, 2022) when compared to the national benchmark (1.0%) for the first time since 2018. Given the significant national problem HA-VTE pose to the public, and the rise in occurrences, this quality improvement (QI) project is clinically relevant.

Post-operative morbidity after neoadjuvant chemotherapy and resection for gallbladder cancer: A national surgical quality improvement program analysis.

BACKGROUND: Gallbladder cancer is the most common malignancy of the biliary tract. Neoadjuvant chemotherapy (NACT) has improved overall survival by enabling R0 resection. Currently, there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer. As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients, we examined American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database to determine if there was higher morbidity among the neoadjuvant group within the 30-day post-operative period. We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity. AIM: To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery. METHODS: A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity (bile leak, infection rate, rate of converting to open surgery, etc.) compared to the group who only had surgery. To calculate the odds ratio for the primary and secondary outcomes, a crude logistic regression was performed. RESULTS: Of the 452 patients, 52 patients received NACT prior to surgery. There were no statistically significant differences in the odds of morbidity between the two groups, including bile leak [odds ratio (OR), 0.69; 95% confidence interval (95%CI): 0.16-2.10; P = 0.55], superficial wound infection (OR, 0.58; 95%CI: 0.03-3.02; P = 0.61), and organ space wound infection (OR, 0.63; 95%CI: 0.18-1.63; P = 0.61). CONCLUSION: There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.

Radiation therapy prior to a pancreaticoduodenectomy for adenocarcinoma is associated with longer operative times and higher blood loss.

BACKGROUND: Pancreatic adenocarcinoma is currently the fourth leading cause of cancer-related deaths in the United States. In patients with "borderline resectable" disease, current National Comprehensive Cancer Center guidelines recommend the use of neoadjuvant chemoradiation prior to a pancreaticoduodenectomy. Although neoadjuvant radiotherapy may improve negative margin resection rate, it is theorized that its administration increases operative times and complexity. AIM: To investigate the association between neoadjuvant radiotherapy and 30-d morbidity and mortality outcomes among patients receiving a pancreaticoduodenectomy for pancreatic adenocarcinoma. METHODS: Patients listed in the 2015-2019 National Surgery Quality Improvement Program data set, who received a pancreaticoduodenectomy for pancreatic adenocarcinoma, were divided into two groups based off neoadjuvant radiotherapy status. Multivariable regression was used to determine if there is a significant correlation between neoadjuvant radiotherapy, perioperative blood transfusion status, total operative time, and other perioperative outcomes. RESULTS: Of the 11458 patients included in the study, 1470 (12.8%) underwent neoadjuvant radiotherapy. Patients who received neoadjuvant radiotherapy were significantly more likely to require a perioperative blood transfusion [adjusted odds ratio (aOR) = 1.58, 95% confidence interval (CI): 1.37-1.82; P < 0.001] and have longer surgeries (insulin receptor-related receptor = 1.14, 95%CI: 1.11-1.16; P < 0.001), while simultaneously having lower rates of organ space infections (aOR = 0.80, 95%CI: 0.66-0.97; P = 0.02) and pancreatic fistula formation (aOR = 0.50, 95%CI: 0.40-0.63; P < 0.001) compared to those who underwent surgery alone. CONCLUSION: Neoadjuvant radiotherapy, while not associated with increased mortality, will impact the complexity of surgical resection in patients with pancreatic adenocarcinoma.

Concurrent major hepatic resection with primary colorectal cancer increases risk of organ space infections.

INTRODUCTION: Patients with colorectal cancer frequently present with liver metastases requiring either concurrent colon and liver resection or staged resection for curative therapy. The goal of this study is to determine if synchronous resection increases risk of perioperative adverse outcomes such as surgical site infections (SSIs). METHODS AND PROCEDURES: We conducted a cross-sectional retrospective analysis of the targeted hepatectomy NSQIP database from 2015 to 2019. The primary outcome was surgical site infections stratified into superficial, deep, organ space, and wound dehiscence. We performed univariate followed by a multivariate logistic regression to determine if there were higher odds of SSIs in patients undergoing hepatic resection concurrently with primary colorectal resection. Additionally, we performed stratified analyses by size of hepatic resections (partial, total left, total right, and trisegmentectomy). RESULTS: Of the 7,445 patients included in the study, 431(5.8%) underwent synchronous resection and 7,014 metachronous resection. On average, synchronous resections prolonged surgery by 62 min. There was no difference in superficial and deep SSIs between the groups; however, there was a significant difference in organ space SSIs. Patients undergoing synchronous resection had 1.51 times the odds of developing an organ space SSI (OR 1.51, 95%CI 1.10, 2.17, p = 0.04) compared to patients with metachronous resection on multivariate analysis. Patients undergoing a total right hepatectomy concurrently with a colorectal resection had 2.30 times the odds of developing an organ space SSI (OR 2.30, 95%CI 1.20, 6.86, p = 0.010). CONCLUSIONS: Prior studies demonstrated that synchronous resections are safe in properly selected patients with no difference in long-term outcomes. Few studies have explored immediate perioperative outcomes between the two approaches. After controlling for confounders, we demonstrate that synchronous resection with major hepatic surgery increases the risk of organ space SSIs. Future studies should elucidate the precise source of organ space SSIs in order to decrease the risk of this adverse outcome.

A Community-Based Pancreatic Cancer Screening Study in High-Risk Individuals: Preliminary Efficacy and Safety Results.

INTRODUCTION: Pancreatic cancer (PC) screening recommendations have been based on studies performed solely at high-volume academic centers. To make PC screening more widely available, community-based efforts are essential. We implemented a prospective PC screening study in the community of Fairfield County, CT, and report our early safety and efficacy results. METHODS: Eligible individuals were enrolled into an investigator-initiated study and underwent a baseline and 3 annual magnetic resonance imagings/magnetic resonance cholangiopancreatographies (MRIs/MRCPs) with gadolinium, biannual blood donations for biobanking, and assessments for anxiety and depression. All MRIs were presented at a multidisciplinary board to determine whether further investigation was warranted. RESULTS: Seventy-five individuals have been enrolled and 201 MRIs performed over a 2.6-year average length of follow-up. Abnormal pancreatic findings (predominantly small cysts) were detected in 58.7% of the participants. Among these, 6.7% underwent endoscopic ultrasound, with 1 case complicated by postprocedural pancreatitis. One surgical resection was performed on a 4.7-cm intraductal papillary mucinous neoplasm with a focus on low-grade pancreatic intraepithelial neoplasia. One incidental finding of fibrosing mediastinitis was detected. Anxiety and depression scores decreased over the course of this study from 21.4% to 5.4% and 10.7% to 3.6%, respectively. DISCUSSION: This preliminary report supports the feasibility of performing MRI/magnetic resonance cholangiopancreatographies-based PC screening as part of a clinical trial in a community setting. A longer follow-up is needed to better assess safety and efficacy. To the best of our knowledge, this is the first report from a community-based PC screening effort ( clinicaltrials.gov ID: NCT03250078).

Gallbladder cancer: Historical treatment and new management options.

Gallbladder cancer is a rare, aggressive malignancy that has a poor overall prognosis. Effective treatment consists of early detection and surgical treatment. With the wide spread treatment of gallbladder disease with minimally invasive techniques, the rate of incidental gallbladder cancer has seen an equitable rise along with stage migration towards earlier disease. Although the treatment remains mostly surgical, newer modalities such as regional therapy as well as directed therapy based on molecular medicine has led to improved outcomes in patients with advanced disease. We aim to summarize the management of gallbladder cancer along with the newer developments in this formidable disease process.

Mortality in hepatectomy: Model for End-Stage Liver Disease as a predictor of death using the National Surgical Quality Improvement Program database.

BACKGROUND: The predictive value of the Model for End-stage Liver Disease (MELD) for mortality after hepatectomy is unclear. This study aimed to evaluate whether MELD score predicts death after hepatectomy and to identify the most useful score type for predicting mortality. We hypothesized that an increase in this score is correlated with 30-day mortality in patients undergoing hepatic resection. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for hepatectomy. Original MELD, United Network of Organ Sharing-modified MELD (uMELD), integrated MELD (i-MELD), and sodium-corrected MELD (MELD-Na) scores were calculated. Mortality was analyzed by multivariate logistic regression. MELD types were compared using receiver operating characteristic (ROC) curves. RESULTS: From 2005 to 2011, 11,933 hepatic resections were performed, including 7,519 partial, 2,104 right, and 1,210 left resections, and 1,100 trisectionectomies. The mean duration of stay was 8.4 ± 22.0 days, and there were 275 deaths (2.4%). The 30-day mortality rates were 1.8%, 6.9%, 15.4%, and 25% according to uMELD strata of 0-9, 10-19, 20-29, and ≥ 30, respectively. Multivariate analysis revealed that increasing MELD stratum was independently associated with higher mortality (P < .001) for all MELD types. The uMELD had the largest effect size (odds ratio [OR], 1.16; 95% CI, 1.10-1.20), whereas i-MELD had the narrowest CI (OR, 1.13; 95% CI, 1.10-1.17) and largest area under the ROC curve. CONCLUSION: The postoperative 30-day mortality after hepatectomy increases with increasing MELD score across all MELD types. There is a 16% increase in the odds of mortality for each point increase in uMELD.

Training and practice of the next generation HPB surgeon: analysis of the 2014 AHPBA residents' and fellows' symposium survey.

BACKGROUND: Hepato-pancreato-biliary (HPB) surgery is a complex subspecialty drawing from varied training pools, and the need for competency is rapidly growing. However, no board certification process or standardized training metrics in HPB surgery exist in the Americas. This study aims to assess the attitudes of current trainees and HPB surgeons regarding the state of training, surgical practice and the HPB surgical job market in the Americas. STUDY DESIGN: A 20-question survey was distributed to members of Americas Hepato-Pancreato-Biliary Association (AHPBA) with a valid e-mail address who attended the 2014 AHPBA. Descriptive statistics were generated for both the aggregate survey responses and by training category. RESULTS: There were 176 responses with evenly distributed training tracks; surgical oncology (44, 28%), transplant (39, 24.8%) and HPB (38, 24.2%). The remaining tracks were HPB/Complex gastrointestinal (GI) and HPB/minimally invasive surgery (MIS) (29, 16% and 7, 4%). 51.2% of respondents thought a dedicated HPB surgery fellowship would be the best way to train HPB surgeons, and 68.1% felt the optimal training period would be a 2-year clinical fellowship with research opportunities. This corresponded to the 67.5% of the practicing HPB surgeons who said they would prefer to attend an HPB fellowship for 2 years as well. Overall, most respondents indicated their ideal job description was clinical practice with the ability to engage in clinical and/or outcomes research (52.3%). CONCLUSIONS: This survey has demonstrated that HPB surgery has many training routes and practice patterns in the Americas. It highlights the need for specialized HPB surgical training and career education. This survey shows that there are many ways to train in HPB. A 2-year HPB fellowship was felt to be the best way to train to prepare for a clinically active HPB practice with clinical and outcomes research focus.

Robotic pancreaticoduodenectomy for pancreatic adenocarcinoma: role in 2014 and beyond.

Minimally invasive surgery (MIS) for pancreatic adenocarcinoma has found new avenues for performing pancreaticoduodenectomy (PD) procedures, a historically technically challenging operation. Multiple studies have found laparoscopic PD to be safe, with equivalent oncologic outcomes as compared to open PD. In addition, several series have described potential benefits to minimally invasive PD including fewer postoperative complications, shorter hospital length of stay, and decreased postoperative pain. Yet, despite these promising initial results, laparoscopic PDs have not become widely adopted by the surgical community. In fact, the vast majority of pancreatic resections performed in the United States are still performed in an open fashion, and there are only a handful of surgeons who actually perform purely laparoscopic PDs. On the other hand, robotic assisted surgery offers many technical advantages over laparoscopic surgery including high-definition, 3-D optics, enhanced suturing ability, and more degrees of freedom of movement by means of fully-wristed instruments. Similar to laparoscopic PD, there are now several case series that have demonstrated the feasibility and safety of robotic PD with seemingly equivalent short-term oncologic outcomes as compared to open technique. In addition, having the surgeon seated for the procedure with padded arm-rests, there is an ergonomic advantage of robotics over both open and laparoscopic approaches, where one has to stand up for prolonged periods of time. Future technologic innovations will likely focus on enhanced robotic capabilities to improve ease of use in the operating room. Last but not least, robotic assisted surgery training will continue to be a part of surgical education curriculum ensuring the increased use of this technology by future generations of surgeons.

Outcomes of surgical resection and loco-regional therapy in patients with stage 3A hepatocellular carcinoma: a retrospective review from the national cancer database.

OBJECTIVES: In advanced stages, hepatocellular carcinoma (HCC) is often associated with major vascular involvement (cava, portal vein). The aim of the present study was to analyse the role of surgical resection (SR) and loco-regional therapy (LRT) in these advanced stage patients to determine if there was a survival benefit. METHODS: The study is a retrospective analysis from the Commission on Cancer's National Cancer Data Base (NCDB) from 1998 to 2011. In total, 148,882 patients with liver cancer were identified, of which 126,984 had HCC. Of these, 64,264 patients (1998-2006) had 5-year survival data available and 8825 patients had Stage 3A disease based on AJCC classification. Of these patients, 884 had SR, 771 had LRT and 7170 patients had neither intervention. Kaplan-Meier curves and log-rank tests were used for statistical analysis. RESULTS: Eight thousand eight hundred and twenty-five patients met analysis criteria. The mean age (years) in the SR, LRT and no intervention group were 62.5, 64.3 and 64.2, respectively. Most patients were males in all three groups (77.5%, 74.5% and 68.1%). The mean tumour size (cm) in the three groups was 9.8, 6.4 and 8.4, respectively. SR and LRT were primarily performed in major academic and comprehensive cancer programmes compared with community cancer programmes and other centres (SR: 93% versus 7%; LRT: 94.6% versus 5.4%). The median 5-year survival (months) was 26.6 in SR, 16.5 in LRT and 4.8 in the no intervention group (P < 0.0001). CONCLUSION: A SR and LRT offer a survival benefit in select patients diagnosed with Stage 3A HCC.

Laparoscopic microwave ablation of human liver tumours using a novel three-dimensional magnetic guidance system.

BACKGROUND: Accurate antenna placement is essential for effective microwave ablation (MWA) of lesions. Laparoscopic targeting is made particularly challenging in liver tumours by the needle's trajectory as it passes through the abdominal wall into the liver. Previous optical three-dimensional guidance systems employing infrared technology have been limited by interference with the line of sight during procedures. OBJECTIVE: The aim of this study was to evaluate a newly developed magnetic guidance system for laparoscopic MWA of liver tumours in a pilot study. METHODS: Thirteen patients undergoing laparoscopic MWA of liver tumours gave consent to their participation in the study and were enrolled. Lesion targeting was performed using the InnerOptic AIM™ 3-D guidance system to track the real-time position and orientation of the antenna and ultrasound probe. RESULTS: A total of 45 ablations were performed on 34 lesions. The median number of lesions per patient was two. The mean ± standard deviation lesion diameter was 18.0 ± 9.2 mm and the mean time to target acquisition was 3.5 min. The first-attempt success rate was 93%. There were no intraoperative or immediate postoperative complications. Over an average follow-up of 7.8 months, one patient was noted to have had an incomplete ablation, seven suffered regional recurrences, and five patients remained disease-free. CONCLUSIONS: The AIM™ guidance system is an effective adjunct for laparoscopic ablation. It facilitates a high degree of accuracy and a good first-attempt success rate, and avoids the line of site interference associated with infrared systems.

Optimal ablation volumes are achieved at submaximal power settings in a 2.45-GHz microwave ablation system.

INTRODUCTION: Local ablative therapies, including microwave ablation (MWA), are common treatment modalities for in situ tumor destruction. Currently, 2.45-GHz ablation systems are gaining prominence because of the shorter application times required. The aims of this study were to determine optimal power and time to ablation volume (AbV) ratios for a new 1.8-mm-2.45-GHz antenna using ex vivo tissue models. METHODS: The 1.8-mm-2.45-GHz Accu2i MWA system was employed to perform ablations in bovine liver, porcine muscle, and porcine kidney ex vivo. Whole tissues were prewarmed (35°C) and multiple ablations performed at power settings of 60 to 180 W for 2- to 6-minute time intervals. Postablation, tissues were dissected, AbVs calculated, and correlations to power and time settings made. RESULTS: Significant increases in AbV were measured between each of the time points for a constant power setting in all 3 tissues. Increasing power settings led to significant increases in AbV at power settings ≤140 W. However, no significant increase in AbV was obtained at power settings >140 W. CONCLUSIONS: Optimal efficiency for MWA using a new 1.8-mm-2.45-GHz system is achieved at settings of ≤140 W for 6 minutes in a range of ex vivo tissue and no additional benefit occurs by increasing the power setting to 180 W in these tissues.

The impact of regionalization of pancreaticoduodenectomy for pancreatic Cancer in North Carolina since 2004.

Pancreaticoduodenectomy (PD) carries a significant risk. High-volume centers (HVCs) provide improved outcomes and regionalization is advocated. Rapid regionalization could, however, have detrimental effects. North Carolina has multiple HVCs, including an additional HVC added in late 2006. We investigated regionalization of PD and its effects before, and after, the establishment of this fourth HVC. The North Carolina Hospital Discharge Database was queried for all PDs performed during 2004 to 2006 and 2007 to 2009. Hospitals were categorized by PD volume as: low (one to nine/year), medium (10 to 19/year), and high (20/year or more). Mortality and major morbidity was assessed by comparing volume groups across time periods. Number of PDs for cancer increased 91 per cent (129 to 246 cases) at HVCs, whereas decreasing at low-volume (62 to 58 cases) and medium-volume (80 to 46 cases) centers. Percentage of PD for cancer performed at HVCs increased significantly (47.6 to 70.3%) while decreasing for low- and medium-volume centers (P < 0.001). Mortality was significantly less at HVCs (2.8%) compared with low-volume centers (10.3%) for 2007 to 2009. Odds ratio for mortality was significantly lower at HVCs during 2004 to 2006 (0.31) and 2007 to 2009 (0.34). Mortality for PD performed for cancer decreased from 6.6 to 4.6 per cent (P = 0.31). Major morbidity was not significantly different between groups within either time period; however, there was a significant increase in major morbidity at low-volume centers (P = 0.018). Regionalization of PD for cancer is occurring in North Carolina. Mortality was significantly lower at HVCs, and rapid regionalization has not detracted from the superior outcomes at HVCs.

Survival analysis of patients with stage I and II hepatocellular carcinoma after a liver transplantation or liver resection.

INTRODUCTION: Liver transplantation (LT) is a treatment option in select patients with hepatocellular carcinoma (HCC). The aim of the present study was to compare survival in Stage I or II HCC patients undergoing either liver transplant (LT) or a liver resection (LR). METHOD: The study is a retrospective analysis of the National Cancer Data Base (1998-2011). In total, 148,882 patients with liver cancer were identified, of which 5-year survival data (1998-2006) were available for 64,227 patients. Patients were stratified by the American Joint Committee on Cancer (AJCC) clinical stage I and II. Kaplan-Meier curves and log-rank tests were used for statistical analysis. RESULTS: 3340 HCC patients met analysis criteria. Among stage I HCC, 860 had LT and 871 had LR. Among stage II HCC, 833 had LT and 776 LR. In stage I patients the median survival for LT and LR were 127.9 and 56.7 months, respectively, (P < 0.0001) and in stage II patients the median survival was 110.8 and 42.8 months (P < 0.0001). Unlike LT patients, LR patients with Stage I HCC had a longer median survival compared with Stage II patients (P = 0.0002). CONCLUSION: Liver transplantation offers a survival advantage compared with a liver resection among patients with Stage I and II HCC. LT is the best surgical treatment for early stage (I/II) HCC in patients with advanced fibrosis or cirrhosis, whereas LR provides equivalent outcomes to LT in patients without advanced fibrosis and should be considered as the first surgical option.

Changes in subcellular distribution of the ammonia transporter, Rhcg, in response to chronic metabolic acidosis.

The primary mechanism by which the kidneys mediate net acid excretion is through ammonia metabolism. In the current study, we examined whether chronic metabolic acidosis, which increases ammonia metabolism, alters the cell-specific and/or the subcellular expression of the ammonia transporter family member, Rhcg, in the outer medullary collecting duct in the inner stripe (OMCDi). Chronic metabolic acidosis was induced in normal SD rats by HCl ingestion for 7 days; controls were pair-fed. The subcellular distribution of Rhcg was determined using immunogold electron microscopy and morphometric analyses. In intercalated cells, acidosis increased total Rhcg, apical plasma membrane Rhcg, and the proportion of total cellular Rhcg in the apical plasma membrane. Intracellular Rhcg decreased significantly, and basolateral Rhcg was unchanged. Because apical plasma membrane length increased in parallel with apical Rhcg immunolabel, apical plasma membrane Rhcg density was unchanged. In principal cells, acidosis increased total Rhcg, apical plasma membrane Rhcg, and the proportion of total cellular Rhcg in the apical plasma membrane while decreasing the intracellular proportion. In contrast to the intercalated cell, chronic metabolic acidosis did not significantly alter apical boundary length; accordingly, apical plasma membrane Rhcg density increased. In addition, basolateral Rhcg immunolabel increased in response to chronic metabolic acidosis. These results indicate that in the rat OMCDi 1) chronic metabolic acidosis increases apical plasma membrane Rhcg in both the intercalated cell and principal cell where it may contribute to enhanced apical ammonia secretion; 2) increased apical plasma membrane Rhcg results from both increased total protein and changes in the subcellular distribution of Rhcg; 3) the mechanism of Rhcg subcellular redistribution differs in intercalated and principal cells; and 4) Rhcg may contribute to regulated basolateral ammonia transport in the principal cell.

Renal expression of the ammonia transporters, Rhbg and Rhcg, in response to chronic metabolic acidosis.

Chronic metabolic acidosis induces dramatic increases in net acid excretion that are predominantly due to increases in urinary ammonia excretion. The current study examines whether this increase is associated with changes in the expression of the renal ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg). Chronic metabolic acidosis was induced in Sprague-Dawley rats by HCl ingestion for 1 wk; control animals were pair-fed. After 1 wk, metabolic acidosis had developed, and urinary ammonia excretion increased significantly. Rhcg protein expression was increased in both the outer medulla and the base of the inner medulla. Intercalated cells in the outer medullary collecting duct (OMCD) and in the inner medullary collecting duct (IMCD) in acid-loaded animals protruded into the tubule lumen and had a sharp, discrete band of apical Rhcg immunoreactivity, compared with a flatter cell profile and a broad band of apical immunolabel in control kidneys. In addition, basolateral Rhcg immunoreactivity was observed in both control and acidotic kidneys. Cortical Rhcg protein expression and immunoreactivity were not detectably altered. Rhcg mRNA expression was not significantly altered in the cortex, outer medulla, or inner medulla by chronic metabolic acidosis. Rhbg protein and mRNA expression were unchanged in the cortex, outer and inner medulla, and no changes in Rhbg immunolabel were evident in these regions. We conclude that chronic metabolic acidosis increases Rhcg protein expression in intercalated cells in the OMCD and in the IMCD, where it is likely to mediate an important role in the increased urinary ammonia excretion.