Synbiotics in Surgery for Chronic Pancreatitis: Are They Truly Effective? A Single-blind Prospective Randomized Control Trial.

BACKGROUND: Postoperative infectious complications in patients undergoing pancreatic surgery are a significant cause for morbidity and mortality. Although synbiotics have beneficial effects on human health, their clinical value in surgical patients remains unclear given a paucity of applicable clinical studies. AIM: To determine the impact of perioperative synbiotic therapy on postoperative infectious complications, morbidity and mortality in patients undergoing pancreatic surgery for chronic pancreatitis. METHODS: A trial was conducted in patients with chronic calcific pancreatitis undergoing Frey's procedure. Group A received a specific synbiotic composition, 5 days prior and 10 days after the surgery. Group B received a placebo. Primary study endpoint was the occurrence of postoperative infection during the first 30 days. Secondary outcome measures were mortality, length of hospital stay, days in intensive care unit, and duration of antibiotic therapy. Using previously accrued data, with α of 0.05 and power 80%, the sample size was calculated as 35 patients for each group with a dropout rate of 10%. RESULTS: Of the 79 patients enrolled, 75 completed the trial [group A (n = 39) and group B (n = 36)]. The incidence of postoperative infectious complications (12.8% vs 39%; P < 0.05), duration of antibiotics therapy (P < 0.05), and length of hospital stay (P < 0.05) were significantly lower in the synbiotic group. CONCLUSIONS: Synbiotics significantly reduce septic complications, hospital stay, and antibiotic requirement in patients undergoing pancreatic surgery for chronic pancreatitis. Furthermore, basic and clinical research would clarify the underlying mechanisms of their therapeutic effect and define the appropriate conditions for use.

Preoperative Platelet-Lymphocyte Ratio Augments CA 19-9 as a Predictor of Malignancy in Chronic Calcific Pancreatitis.

INTRODUCTION: Differentiating inflammatory from malignant head mass in the background of chronic calcific pancreatitis (CCP) is difficult, and there is no investigation which can reliably solve this dilemma. An accurate diagnosis is crucial as the treatment is different for the two cases and a failure to identify malignancy before surgery can be disastrous. We aimed to assess the accuracy of platelet-lymphocyte ratio (PLR) and to compare it with CA 19-9 in determining the nature of pancreatic head mass (PHM). MATERIALS AND METHODS: Eighty-three patients, who presented with CCP and PHM between 2005 and 2011, were included in the study. Patients identified to have malignancy underwent pancreaticoduodenectomy, while those deemed to have a benign lesion underwent Frey's procedure. Clinical features of both the groups were compared. CA 19-9 and PLR individually and in combination were compared in both groups. Receiver operating characteristic curves were used to analyze the predictive values of CA 19-9 and PLR individually and together. RESULTS: Histologically, 66.3% had an inflammatory head mass and 33.7% had a malignant head mass. Significant clinical features which predicted a malignancy included the presence of a head mass in CCP of tropics, older age, jaundice, sudden worsening abdominal pain, gastric outlet obstruction, and significant weight loss. Sensitivity and specificity of CA 19-9 and PLR in diagnosing malignancy were similar (85.5 vs. 81.2 and 96.4 vs. 92.8%, respectively), on combining CA 19-9 and PLR, there was an improvement in sensitivity (94.5%). CONCLUSION: PLR is at least as good as CA 19-9 as a diagnostic marker to differentiate between malignant and inflammatory head mass in CCP. When used together, PLR improves the predictive value of serum CA 19-9.

Bile duct thrombi in hepatocellular carcinoma: is aggressive surgery worthwhile?

INTRODUCTION: Obstructive jaundice as a result of bile duct tumour thrombus (BDTT) is an unusual clinical entity and an uncommon presenting feature of hepatocellular carcinoma (HCC). This study evaluates the outcome of hepatectomy for HCC with obstructive jaundice as a result of BDTT in non-cirrhotic livers. METHODS: Between 1997 and 2012, out of 426 patients with HCC in non-cirrhotic livers, 39 patients with BDTT (Group I n = 39), who underwent a hepatectomy, were analysed and compared with the non-BDTT group (Group II n = 387). RESULTS: The demographic profile and biochemical parameters between Group I and Group II were compared; apart from the presence of jaundice at presentation and an elevated serum bilirubin, there were no significant differences. Post-operative morbidity and mortality were 11 (28.2%) and 2 (5.1%), respectively, in Group I. There were no differences between the groups with regards to the operative variables and short-term outcomes. The 1-, 3- and 5-year survival rates in Group I were 82%, 48% and 10%, respectively, with a median survival of 28.6 months and were significantly poorer than Group II (90%, 55% and 38%, respectively, with a median survival of 39.2 months). CONCLUSION: The mere presence of BDTT in HCC does not indicate an advanced or inoperable lesion. When technically feasible, a formal hepatic resection is the preferred first-line treatment option in these patients.

Massive hemobilia: a diagnostic and therapeutic challenge.

BACKGROUND: Massive hemobilia is a rare but potentially life-threatening cause of upper gastrointestinal hemorrhage. In this retrospective analysis, we have evaluated the challenges involved in the diagnosis and management of massive hemobilia. METHODS: Between 2001 and 2011, a total of 20 consecutive patients (14 males) who were treated in our department for massive hemobilia were included in the study and their records were retrospectively analyzed. RESULTS: Causes of hemobilia were blunt liver trauma (n = 9), hepatobiliary intervention (n = 4), post-laparoscopic cholecystectomy hepatic artery pseudoaneurysm (n = 3), hepatobiliary tumors (n = 3), and vascular malformation (n = 1). Melena, abdominal pain, hematemesis, and jaundice were the leading symptoms. All patients had undergone upper GI endoscopy, abdominal ultrasound, and computerized tomography of the abdomen. An angiogram and therapeutic embolization were done in 12 patients and was successful in nine but failed in three, requiring surgery. Surgical procedures performed were right hepatectomy (n = 4), extended right hepatectomy (n = 1), segmentectomy (n = 1), extended cholecystectomy (n = 1), repair of the pseudoaneurysm (n = 3), and right hepatic artery ligation (n = 1). CONCLUSION: The successful diagnosis of hemobilia depends on a high index of suspicion for patients with upper GI bleeding and biliary symptoms. Although transarterial embolization is the therapeutic option of choice for massive hemobilia, surgery has a definitive role in patients with hemodynamic instability, after failed embolization, and in patients requiring laparotomy for other reasons.

Transpancreatic hepatomesenteric trunk complicating pancreaticoduodenectomy.

CONTEXT: Standard celiac and hepatic arterial anatomy occur in approximately 60% of the patients; for the remaining, multiple variations have been described. A thorough knowledge of these anomalies is important in order to avoid unnecessary complications. In this report we describe one of the rarest arterial anomalies, a hepatomesenteric trunk supplying the liver. We attempt to elucidate its implications pertaining to the safe performance of a pancreaticoduodenectomy. CASE REPORT: A 45-year-old male with a one-month duration painless progressive jaundice was evaluated and diagnosed as having a periampullary growth. Preoperative imaging did not suggest any arterial anomalies. Intraoperatively, the common hepatic artery was found to originate from the superior mesenteric artery. He underwent a pylorus preserving pancreaticoduodenectomy with a meticulous dissection and preservation of the aberrant hepatomesenteric trunk. His postoperative period was uneventful and is doing well on follow up. CONCLUSION: Variations in hepatic and celiac arterial anatomy are common, and may not get picked up on preoperative imaging. A high index of suspicion in every patient along with a precise knowledge of the normal anatomy and awareness of the aberrant anatomy is a sine qua non to the performance of a safe pancreaticoduodenectomy.

Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells.

Ghrelin, a recently described endogenous ligand for the growth hormone secretagogue receptor (GHS-R), is produced by stomach cells and is a potent circulating orexigen, controlling energy expenditure, adiposity, and growth hormone secretion. However, the functional role of ghrelin in regulation of immune responses remains undefined. Here we report that GHS-R and ghrelin are expressed in human T lymphocytes and monocytes, where ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6, and TNF-alpha. Ghrelin led to a dose-dependent inhibition of leptin-induced cytokine expression, while leptin upregulated GHS-R expression on human T lymphocytes. These data suggest the existence of a reciprocal regulatory network by which ghrelin and leptin control immune cell activation and inflammation. Moreover, ghrelin also exerts potent anti-inflammatory effects and attenuates endotoxin-induced anorexia in a murine endotoxemia model. We believe this to be the first report demonstrating that ghrelin functions as a key signal, coupling the metabolic axis to the immune system, and supporting the potential use of ghrelin and GHS-R agonists in the management of disease-associated cachexia.

Xanthogranulomatous cholecystitis masquerading as gallbladder cancer: can it be diagnosed preoperatively?

Background. Xanthogranulomatous cholecystitis (XGC) is often misdiagnosed as gallbladder cancer (GBC). We aimed to determine the preoperative characteristics that could potentially aid in an accurate diagnosis of XGC masquerading as GBC. Methods. An analysis of patients operated upon with a preoperative diagnosis of GBC between January 2008 and December 2012 was conducted to determine the clinical and radiological features which could assist in a preoperative diagnosis of XGC. Results. Out of 77 patients who underwent radical cholecystectomy, 16 were reported as XGC on final histopathology (Group A), while 60 were GBC (Group B). The incidences of abdominal pain, cholelithiasis, choledocholithiasis, and acute cholecystitis were significantly higher in Group A, while anorexia and weight loss were higher in Group B. On CT, diffuse gallbladder wall thickening, continuous mucosal line enhancement, and submucosal hypoattenuated nodules were significant findings in Group A. CT findings on retrospect revealed at least one of these findings in 68.7% of the cases. Conclusion. Differentiating XGC from GBC is difficult, and a definitive diagnosis still necessitates a histopathological examination. An accurate preoperative diagnosis requires an integrated review of clinical and characteristic radiological features, the presence of which may help avoid radical resection and avoidable morbidity in selected cases.

Incidental gall bladder cancers: Are they truly incidental?

AIM: To seek and analyze features suggestive of gallbladder cancer (GBC) on preoperative imaging and intraoperative findings in patients diagnosed as having incidental GBC (IGBC). METHODS: The study was conducted on 79 patients of IGBC managed in our department over a 10-year period (2003-2012). Review of preoperative imaging and operative notes was done to ascertain any suspicion of malignancy-in-retrospect. RESULTS: Of the 79 patients, Ultrasound abdomen showed diffuse thickening, not suspicious of malignancy in 5 patients, and diffuse suspicious thickening was seen in 4 patients. Focal thickening suspicious of malignancy was present in 24 patients. Preoperative computed tomography/magnetic resonance imaging was done in 9 patients for suspicion of malignancy. In 5 patients, difficult Cholecystectomy was encountered due to dense/inflammatory adhesions. Intraoperative findings showed focal thickening of the gallbladder and a gallbladder mass in 9 and 17 patients respectively. On overall analysis, 37 patients had preoperative imaging or intraoperative findings suggestive of malignancy, which was either a missed GBC or an unsuspected/unexpected GBC. In 42 (53.2%) patients, there was no evidence suggestive of malignancy and was an unanticipated diagnosis. CONCLUSION: Our study highlights a potential and not-so-rare pitfall of Laparoscopic Cholecystectomy. A greater awareness of this clinical entity along with a high index of suspicion and a low threshold for conversion to open procedure, especially in endemic areas may avert avoidable patient morbidity and mortality.

Outcome of video-assisted translumbar retroperitoneal necrosectomy and closed lavage for severe necrotizing pancreatitis.

INTRODUCTION AND OBJECTIVE: Surgery for necrotizing pancreatitis is associated with a high rate of morbidity and mortality. We present a series of 26 patients who underwent video-assisted translumbar retroperitoneal necrosectomy and analyse their outcomes. METHODS: Records of 26 patients who underwent video-assisted translumbar retroperitoneal necrosectomy and closed drainage for infected pancreatitic necrosis between January 2008 and March 2012 were reviewed, retrospectively. RESULTS: Twenty-three out of 26 patients were males, with a mean age of 38.6 (±9.9) years. Alcohol was the aetiology in 18 patients, gall stones in 7, and in 1 it was idiopathic. The mean duration of symptoms before patients were taken up for surgery was 47.2 (±34.8) days. The mean computed tomography severity index was 7.7 (±1.2). All patients had undergone video-assisted retroperitoneal necrosectomy through a limited left lumbar incision. Post-operative lavage was given through drains placed in the retroperitoneum. Three patients required re-exploration. Eleven patients developed complications and there were two mortalities. The median intensive care unit (ICU) stay was 4 days (range 2-14 days). The mean post-operative hospital stay was 22.5 (±6.6) days. CONCLUSION: Video-assisted translumbar retroperitoneal necrosectomy followed by closed lavage of infected pancreatic necrosis in select cases of infected pancreatic necrosis was associated with a low rate of ICU stay, hospital stay and need for re-entry.

Feasibility of implementing fast-track surgery in pancreaticoduodenectomy with pancreaticogastrostomy for reconstruction--a prospective cohort study with historical control.

INTRODUCTION: Fast track programmes have been introduced in pancreatic surgery, but the data are sparse. The aim of this prospective study was to analyse the feasibility of implementing fast track rehabilitation protocol in PD with pancreaticogastrostomy, using historical control for comparison. MATERIALS AND METHODS: Between April 2012 and December 2012, twenty patients who underwent PD (with pancreaticogastrostomy) were managed by a fast-track rehabilitation protocol. These patients were compared with an equal number of historical controls treated according to the traditional protocol. RESULTS: Patients in the fast track group were able to tolerate liquid (p = 0.0005) and solid diet (p = 0.0001) earlier, and they passed stools earlier (p = 0.02). Delayed gastric emptying (DGE) was significantly reduced in the fast track group (p = 0.02). There was no difference in the rates of pancreatic fistula (PF), post pancreatectomy haemorrhage (PPH) and mortality between the two groups. Length of hospital stay was reduced in the fast track group (median 14 vs 18.5, p = 0.007). CONCLUSION: Fast track programme appears to be feasible in PD, even with pancreatico-gastric anastomosis. It is associated with early recovery, reduced DGE and reduced hospital stay.

Implications of the presence of an aberrant right hepatic artery in patients undergoing pancreaticoduodenectomy.

AIM: To analyze the differences in outcomes and the clinical impact following pancreatoduodenectomy (PD) in patients with and without aberrant right hepatic artery (aRHA). METHODS: All patients undergoing PD between January 2008 and December 2012 were divided into two groups, one with aRHA and the other without. These groups were compared to identify differences in the intraoperative variables, the oncological clearance and the postoperative morbidity, mortality and hospital stay. RESULTS: A total of 225 patients underwent PD, of which 43 (19.1%) patients were found to have either accessory or replaced right hepatic arteries (aRHA group). The aRHA was preserved in 79% of the patients. There was no significant difference in the intraoperative blood loss but operative time was prolonged, reflecting the complexity of the procedure [420 ± 44 (240-540) min vs 480 ± 45 (300-600) min, P < 0.05)]. There were no differences in the incidence of postoperative complications (pancreatic leak, pancreatic fistula, delayed gastric emptying and mortality) and hospital stay. Oncological clearance in the form of positive resection margins [13 (7.1%) vs 3 (6.9%)] and lymph node yield were also similar in the two groups. CONCLUSION: An aRHA is found in approximately one fifth of patients undergoing PD. Preservation is technically possible in most patients and can increase the operative complexity but does not negatively affect the safety or oncological outcomes of the procedure.

Impact of perioperative enteral synbiotics in hepatic and pancreatic surgery: design and rationale of a single blind placebo controlled prospective randomised control trial.

BACKGROUND: Prebiotics and probiotics influence all pathogenic mechanisms of bacterial translocation. Used in combination, they are called synbiotics. Postoperative infective complications in patients undergoing hepatic and pancreatic surgery lead to a significant prolongation of hospital stay and increased costs. While synbiotics are considered to have beneficial effects on human health, their clinical value in surgical patients, especially in South Asia remains unclear given a paucity of applicable clinical studies. In this study we aim to assess their clinical usefulness in patients who undergo hepatic and pancreatic surgery. METHODS: A prospective monocentric randomised single blind controlled trial is being conducted in patients undergoing major pancreatic resections (Whipple procedure, distal pancreatectomy, Frey procedure) and hepatic resections. Group A received a specific synbiotic composition, 5 days prior and 10 days after the surgery. Group B received a placebo. Primary study end point was the occurrence of postoperative infection during the first 30 days. Secondary outcome measures were mortality, first bowel movement, days in intensive care unit, length of hospital stay, and duration of antibiotic therapy. Side effects of probiotics were evaluated. From previous studies we assumed that perioperative synbiotics reduce the proportion of patients with infectious complications from 50% to 12%, with α of 0.05 and power 80%, the calculated sample size was 35 patients for each group with a dropout rate of 10%. CONCLUSIONS: This study is intended at determining the impact of perioperative synbiotic therapy on postoperative infectious complications, morbidity and mortality in patients undergoing major pancreatic and hepatic surgery. CLINICAL TRIAL: The Clinical Trials Registry of India (CTRI/2013/06/003737).

Predictors of malignancy in chronic calcific pancreatitis with head mass.

AIM: To prospectively analyse the clinical, biochemical and radiological characteristics of the mass lesions arising in a background of chronic calcific pancreatitis (CCP). METHODS: Eighty three patients, who presented with chronic pancreatitis (CP) and a mass lesion in the head of pancreas between February 2005 and December 2011, were included in the study. Patients who were identified to have malignancy underwent Whipple's procedure and patients whose investigations were suggestive of a benign lesion underwent Frey's procedure. Student t-test was used to compare the mean values of imaging findings [common bile duct (CBD), main pancreatic duct (MPD) size] and laboratory data [Serum bilirubin, carbohydrate antigen 19-9 (CA 19-9)] between the groups. Receiver operating characteristic curve (ROC curve) analysis was done to calculate the cutoff valves of serum bilirubin, CA 19-9, MPD and CBD size. The sensitivity, specificity, positive predictive valve (PPV) and negative predictive value (NPV) were calculated using these cut off points. Multivariate analysis was performed using logistic regression model. RESULTS: The study included 56 men (67.5%) and 27 women (32.5%). Sixty (72.3%) patients had tropical calcific pancreatitis and 23 (27.7%) had alcohol related CCP. Histologically, it was confirmed that 55 (66.3%) of the 83 patients had an inflammatory head mass and 28 (33.7%) had a malignant head mass. The mean age of individuals with benign inflammatory mass and those with malignant mass was 38.4 years and 45 years respectively. Significant clinical features that predicted a malignant head mass in CP were presence of a head mass in CCP of tropics, old age, jaundice, sudden worsening abdominal pain, gastric outlet obstruction and significant weight loss (P ≤ 0.05). The ROC curve analysis showed a cut off value of 5.8 mg/dL for serum bilirubin, 127 U/mL for CA 19-9, 11.5 mm for MPD size and 14.5 mm for CBD size. CONCLUSION: Elevated Serum bilirubin and CA 19-9, and dilated MPD and CBD were useful in predicting malignancy in patients with CCP and head mass.

Isolated caudate lobe resection: technical challenges.

BACKGROUND: Isolated caudate lobe resection remains a technical challenge even in the best hands. This is due to the difficult approach and its location between major vessels. This retrospective study aims to analyze our experience with isolated caudate lobe resections. METHODS: Of the 402 patients who underwent liver resections between January 2002 and December 2011, we identified 13 caudate lobectomies. We analyzed the operative parameters, hospital stay, morbidity and follow up of these patients. RESULTS: There were nine males and four females, age ranging between 30 and 72 years. The indications were hepatocellular carcinoma in nine patients, hilar cholangiocarcinoma in two, solitary fibrous tumor in one, and a regenerative nodule in one patient. Left-sided approach was employed in seven cases, right-sided approach in three cases and a combined approach in three cases. Operating time ranged between 125 and 225 min and blood loss ranged between 210 and 630 mL. There was no mortality in the post-operative period. No local recurrence was noted in the follow-up period ranging from 6 months to 7 years. CONCLUSION: Caudate lobe resections, although technically challenging, can be successfully performed with minimal blood loss. Surgery offers potential cure in isolated caudate lobe tumors. The location and size of the tumor decides the approach.

A gist of gastrointestinal stromal tumors: A review.

Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mesenchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularly-targeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.

Hemosuccus Pancreaticus: 15-Year Experience from a Tertiary Care GI Bleed Centre.

Background. Hemosuccus pancreaticus (HP) is a very rare and obscure cause of upper gastrointestinal bleeding. Due to its rarity, the diagnostic and therapeutic strategy for the management of this potentially life threatening problem remains undefined. The objective of our study is to highlight the challenges in the diagnosis and management of HP and to formulate a protocol to effectively and safely manage this condition. Methods. We retrospectively reviewed the records of all patients who presented with HP over the last 15 years at our institution between January 1997 and December 2011. Results. There were a total of 51 patients with a mean age of 32 years. Nineteen patients had chronic alcoholic pancreatitis; twenty-six, five, and one patient had tropical pancreatitis, acute pancreatitis, and idiopathic pancreatitis, respectively. Six patients were managed conservatively. Selective arterial embolization was attempted in 40 of 45 (89%) patients and was successful in 29 of the 40 (72.5%). 16 of 51 (31.4%) patients required surgery. Overall mortality was 7.8%. Length of followup ranged from 6 months to 15 years. Conclusions. Upper gastrointestinal bleeding in a patient with a history of chronic pancreatitis could be caused by HP. All hemodynamically stable patients with HP should undergo prompt initial angiographic evaluation, and if possible, embolization. Hemodynamically unstable patients and those following unsuccessful embolization should undergo emergency haemostatic surgery. Centralization of GI bleed services along with a multidisciplinary team approach and a well-defined management protocol is essential to reduce the mortality and morbidity of this condition.

Biliary cystadenomas: a case for complete resection.

Introduction and Objective. Biliary cystadenoma is a rare benign neoplasm of the liver with less than 200 cases being reported allover the world. We report a series of 13 cases highlighting the radiological findings and problems related to its management. Materials and Methods. Records of thirteen patients who underwent surgery for biliary cystadenomas, between March 2006 and October 2011, were reviewed retrospectively. Results. Majority of the patients were females (11 out of 13), with a median age of 46 (23-65) years. The most frequent symptom was abdominal pain (92%). Seven patients had presented with history of previous surgery for liver lesions. Five patients had presented with recurrence after partial resection for a suspected hydatid cyst and two after surgery for presumed simple liver cyst. Ten of the 13 patients had complete resection of the cyst with enucleation in 3 patients, 2 of whom in addition required T-tube drainage of the bile duct. There has been no recurrence during the follow-up period ranging from 3 months to 5 years. Conclusion. Biliary cystadenoma must be differentiated from other benign cysts. Hepatic resection or cyst enucleation is the recommended treatment option.

CCL5 modulates pneumococcal immunity and carriage.

Understanding the requirements for protection against pneumococcal carriage and pneumonia will greatly benefit efforts in controlling these diseases. Recently, it has been shown that genetic polymorphisms can result in diminished expression of CCL5, which results in increased susceptibility to and progression of infectious diseases. We show that CCL5, together with Th cytokine mRNA expression, is temporally up-regulated during pneumococcal carriage. To determine the contribution of CCL5 to pneumococcal surface antigen A-specific humoral and cellular pneumococcal immunity, mice were treated with anti-CCL5 or control Abs before and during Streptococcus pneumoniae strain EF3030-challenge for the initiation of carriage. CCL5 blockade resulted in a decrease of CD4(+) and CD8(+) T cells as well as CD11b(+) cells in the spleen, cervical lymph node, lung, and nasopharyngeal associated lymphoid tissue during the recognition phase of the pneumococcal adaptive immune response. CCL5 blockade significantly reduced the Ag-specific IgG2a and IgG1 Abs in serum and IgA Ab levels in nasal washes. These decreases also corresponded to reductions in Ag-specific T cell (mucosal and systemic) responses. CCL5 inhibition resulted in decreasing the quantity of IL-4- and IFN-gamma-secreting CD4(+) T cells and increasing the number of Ag-specific IL-10-producing CD4(+) T cells; these changes combined also corresponded with the transition from pneumococcal carriage to lethal pneumonia. These data suggest that CCL5 is an essential factor for the induction and maintenance of protective pneumococcal immunity.