Changes in mandibular position during midface distraction in patients with syndromic craniosynostosis.

The purpose of this study was to evaluate changes in mandibular position during midface distraction. Midface distraction was performed in patients with syndromic craniosynostosis to increase upper airway volume. Although this treatment resulted in changes in occlusion, the concomitant changes in mandibular position were poorly understood. In this retrospective study, three-dimensional (3D) cephalograms were obtained before and after midface distraction in 15 patients with syndromic craniosynostosis. Perioperative polysomnography scores and changes in maxillary and mandibular position, mandibular volume, and upper airway volume were analyzed. Results showed a significant improvement in apnea-hypopnea index (AHI) (from 20.6 ± 21.3 to 6.9 ± 5.1, p < 0.05) and upper airway volume (from 2951.65 ± 2286.38 to 5218.04 ± 3150.05 mm3, p < 0.001). When the lowest point of the sella turcica was set as the reference point, the mandible moved significantly in an anterior direction (from 47.9 ± 11.5 to 51.9 ± 9.8 mm, p < 0.05). Mandibular volume did not change significantly perioperatively (from 32530.19 ± 10726.01 to 35590.50 ± 14879.21 mm3, p = 0.10). There were positive correlations between the rates of improvement in AHI and the amount of mandibular movement in the anterior and inferior directions (both p < 0.05). Within the limitations of the study, it seems that the mandible moved in the anterior-inferior direction after midface distraction, and the amount of movement correlated with improvement in respiratory function. Therefore, it is important to consider the position of the mandible when determining the direction of midface distraction, as it may influence the therapeutic effect.

Fertility-sparing Scrotal Reconstruction with a Superficial Circumflex Iliac Perforator Flap.

It is believed that skin flaps should not be used to reconstruct large scrotal defects because thick flaps increase testicular temperature and decrease fertility, and those skin grafts should be used to reconstruct large scrotal defects. We report a case of extensive scrotal defect reconstructed with bilateral superficial circumflex iliac perforator (SCIP) flaps in which spermatogenesis improved postoperatively over time. A 44-year-old man underwent reconstruction of an extensive scrotal defect caused by Fournier gangrene, and bilateral SCIP flaps were used for the reconstruction. In the third postoperative month, his semen volume and sperm count after centrifugation were 1.5 mL and eight, respectively. Based on these semen findings, fertility specialists diagnosed the patient with extremely low fertility. In the ninth postoperative month, the semen volume was 2.2 mL, sperm density was 2.7 × 106/mL, sperm motility was 64%, and normal sperm morphology was 54%, indicating significant improvement. Based on the sperm findings, fertility specialists considered the patient capable of causing pregnancy. There have been no reports of preservation of spermatogenesis after scrotal reconstruction with a thinned perforator flap. In the postoperative period, we observed improvement of spermatogenesis, which suggests that scrotal reconstruction with an SCIP flap may be effective for improving both cosmetic appearance and fertility.

Scarless Donor Site for Breast Reconstruction by Endoscopy-assisted Extended Latissimus Dorsi Flap plus Lipofilling.

BACKGROUND: Breast reconstruction using endoscopy-assisted latissimus dorsi (LD) flap leaves no scar on the back; however, the small amount of tissue obtained makes this procedure less practical. This study aimed to propose a new technique of endoscopy-assisted extended LD (eeLD) flap plus lipofilling, which could secure a large breast volume. METHODS: Lateral thoracic adipose tissues supplied by the thoracodorsal artery branches and the LD muscle were elevated as a single unit only through the mastectomy scar and three ports through the lateral chest. Further, fat was simultaneously injected to support the volume and shape of the breast. Changes in the volume of the reconstructed breast over time were measured using three-dimensional stereophotogrammetry. RESULTS: Overall, 15 breasts of 14 patients who underwent breast reconstruction using an eeLD flap exhibited no serious complications. On average, 281.9 ± 32.4 g of flap and 74.7 ± 19.4 ml of lipofilling were used. Within 8 weeks after the procedure, the volume of the reconstructed breast decreased to 69.5% ± 7.5% and then plateaued. Seven patients needed a subsequent session of lipofilling to acquire adequate breast volume and projection. Notably, according to the BREAST-Q back scores, patients who underwent eeLD flap were significantly more satisfied than those who underwent conventional LD musculocutaneous flap using a skin paddle on the back at the same institution (82.8 ± 9.2 vs. 62.6 ± 6.3, P < 0.0001). CONCLUSION: Despite the limitations in volume, eeLD flap plus lipofilling is advantageous because it does not leave a noticeable donor site scar.

Factors affecting technical success of endoscopic transpapillary gallbladder drainage for acute cholecystitis.

BACKGROUND/PURPOSE: Endoscopic transpapillary gallbladder drainage (ETGBD), including endoscopic nasogallbladder drainage (ENGBD) and endoscopic gallbladder stenting (EGBS), has been reported to be an effective treatment for acute cholecystitis. However, ETGBD is considered to be more difficult than percutaneous transhepatic gallbladder drainage (PTGBD), and few studies have evaluated the factors that affect technical success of the procedure. We investigated the factors predicting its technical success from among patient characteristics and image findings before treatment. METHODS: Three hundred twenty three patients who underwent ETGBD for acute cholecystitis from November 2006 to December 2018 were analyzed retrospectively. RESULTS: The technical success rate was 72.8% (235/323). The technical success rate by cystic duct direction was as follows: proximal/distal, 65.9%/93.6%; right/left: 74.0%/65.2%; cranial/caudal, 83.5%/20.0%. The clinical response rate was 96.2% (226/235). Adverse events were encountered in 5.9% of cases (19/323), including cystic duct injury (11 patients), pancreatitis (five patients), and bleeding (three patients). In both univariate and multivariate analysis, presence of cystic duct stone, dilation of the common bile duct (CBD), and cystic duct direction (proximal and caudal branches) were identified as significant factors affecting technical failure of ETGBD. CONCLUSION: Although ETGBD was an effective and safe procedure for acute cholecystitis, it has a limited success rate. The presence of cystic duct stone, dilation of CBD, and cystic duct direction (proximal and caudal branches) can serve as important predictors of ETGBD difficulties. These findings should be considered before procedures and the necessary adaptation of ETGBD made.

Second-Line Gemcitabine Plus Nab-Paclitaxel for Patients with Unresectable Advanced Pancreatic Cancer after First-Line FOLFIRINOX Failure.

FOLFIRINOX (FX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have been reported as effective regimens for unresectable advanced pancreatic cancer (APC). FX may be more effective but is also associated with more adverse events (AEs). Therefore, first-line treatment with FX followed by second-line GnP may be appropriate. AIMS: To assess the safety and efficacy of second-line GnP for patients with APC after first-line FX failure. METHODS: This study was a multicenter prospective phase II study evaluating second-line GnP in patients with APC after failed first-line FX. The primary endpoint was response rate (RR), and the secondary endpoints were overall survival (OS), progression free survival (PFS), and the frequency and degree of adverse events (AEs). RESULTS: Thirty patients (14 male; median age, 64 years) were enrolled. The RR was 13.3%, with a median follow-up time of 9.3 months. The median OS and PFS were 7.6 and 3.8 months, respectively. From the beginning of first-line treatment, the median OS and PFS were 14.2 and 9.3 months, respectively. Grade 3 or 4 AEs were seen in 70% of patients. CONCLUSION: Second-line GnP after FX failure for patients with APC could be more effective than GEM alone. Further comparison studies are warranted.

Modulation of Diacylglycerol-Induced Melanogenesis in Human Melanoma and Primary Melanocytes: Role of Stress Chaperone Mortalin.

Skin color/pigmentation is regulated through melanogenesis process in specialized melanin-producing cells, melanocytes, involving multiple signaling pathways. It is highly influenced by intrinsic and extrinsic factors such as oxidative, ultraviolet radiations and other environmental stress conditions. Besides determining the color, it governs response and tolerance of skin to a variety of environmental stresses and pathological conditions including photodamage, hyperpigmentation, and skin cancer. Depigmenting reagents have been deemed useful not only for cosmetics but also for pigmentation-related pathologies. In the present study, we attempted modulation of 1-oleoyl-2-acetyl-glycerol- (OAG-) induced melanogenesis in human melanoma and primary melanocytes. In both cell types, OAG-induced melanogenesis was associated with increase in enhanced expression of melanin, tyrosinase, as well as stress chaperones (mortalin and HSP60) and Reactive Oxygen Species (ROS). Treatment with TXC (trans-4-(Aminomethyl) cyclohexanecarboxylic acid hexadecyl ester hydrochloride) and 5/40 natural compounds resulted in their reduction. The data proposed an important role of mortalin and oxidative stress in skin pigmentation and the use of TXC and natural extracts for modulation of pigmentation pathways in normal and pathological conditions.

A case of liver hilar tuberculous lymphadenitis complicated by biliary stricture diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

This report describes a case of liver hilar tuberculous lymphadenitis complicated by biliary stricture, diagnosed with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). A 44-year-old woman was referred to our center for further evaluation of abnormal liver function tests. Abdominal ultrasound/contrast-enhanced computed tomography (CT) revealed a 15-mm hypovascular mass with a weakly enhanced margin at the liver hilum. Magnetic resonance cholangiopancreatography revealed dilatation of the intrahepatic bile ducts in the left lobe of liver and gradual narrowing of the left hepatic duct. Biliary stricture associated with enlarged hilar lymph nodes due to metastasis or malignant lymphoma was suspected, but calcification on chest CT and a positive T-SPOT test did not rule out tuberculosis. After transpapillary brush cytology of the bile duct stricture failed to confirm the diagnosis, EUS-FNA of hilar lymph nodes was performed and showed positive for the acid-fast bacillus and polymerase chain reaction for Mycobacterium tuberculosis DNA as well as epithelioid granulomas on pathological evaluation. Those findings led to a diagnosis of hilar tuberculous lymphadenitis. The patient is under treatment with antituberculosis drugs. Abdominal tuberculous lymphadenitis is rare and some cases diagnosed as lymphadenopathy of unknown origin have required surgery. EUS-FNA is a safe and minimally invasive diagnostic method in such cases.

Hybrid procedure combining endoscopic gallbladder lavage and internal drainage with elective cholecystectomy for acute cholecystitis: A prospective pilot study (The BLADE study).

BACKGROUND AND AIM: Percutaneous transhepatic drainage is the most common method for non-operative gallbladder drainage, but the technique does have several disadvantages because of its invasive nature and requirement for continuous drainage. To overcome these disadvantages, we developed a novel procedure, endoscopic gallbladder lavage followed by stent placement, carried out in a single endoscopic session. Our aim was to prospectively evaluate the efficacy and safety of this procedure in patients with acute cholecystitis. METHODS: Patients diagnosed with moderate cholecystitis at four tertiary care centers were enrolled in this study. We initially placed a 5-Fr tube to carry out gallbladder lavage. The tube was then cut to the optimal length and placed as a stent. Main outcomes were procedural and clinical success rates. RESULTS: The procedure was attempted in 40 patients and was successful in 30 (75.0%). Minor adverse events occurred in two (5.0%) patients: perforation of the cystic duct by the guidewire in one patient and pancreatitis in the other. Among the 30 patients in whom the procedure was successfully done, clinical resolution was obtained in 29 (96.6%). Elective cholecystectomy was carried out in 37 patients (92.5%), with a median delay after drainage of 42 days (range, 12-138 days). There were no adverse events during the waiting period. CONCLUSIONS: Gallbladder rinsing followed by internal drainage using a 5-Fr nasobiliary tube is considered an effective and safe alternative to other techniques, providing an acceptable success rate in patients with acute cholecystitis prior to elective surgery. CLINICAL TRIAL INFORMATION: http://www.umin.ac.jp/ctr/index.htm (ID: UMIN-000009680).

A multicenter prospective phase II study of first-line modified FOLFIRINOX for unresectable advanced pancreatic cancer.

BACKGROUND: FOLFIRINOX (FX) has been reported as an effective treatment for unresectable advanced pancreatic cancer. However, FX is associated with a high incidence of adverse events (AEs). A previous phase II study in Japan showed high incidences of hematological AEs, including febrile neutropenia (22.2%). A modified FX regimen (mFX) may decrease the rates of AEs and be more effective than FX by improving the treatment compliance. AIMS: To assess the safety and efficacy of first-line mFX for unresectable advanced pancreatic cancer. PATIENTS AND METHODS: This was as a multicenter prospective phase II study in chemotherapy-naïve Japanese patients with pathologically confirmed unresectable advanced pancreatic adenocarcinoma or adenosquamous carcinoma. Treatment with mFX (85 mg/m2 oxaliplatin, 150 mg/m2 irinotecan, and 200 mg/m2 l-leucovorin, followed by 46-h continuous infusion of 2400 mg/m2 5-fluorouracil) was administered every 2 weeks. The primary endpoint was the response rate. The secondary endpoints were overall survival, progression-free survival, and safety. RESULTS: Thirty-one patients (18 men; median age, 64 years) were enrolled. A median of 13 treatment cycles were administered during a median follow-up period of 14.2 months. The response rate, median overall survival, and median progression-free survival were 38.7%, 14.9 months, and 7.0 months, respectively. Grade 3 or 4 AEs included neutropenia (83.9%), febrile neutropenia (16.1%), peripheral sensory neuropathy (9.7%), thrombocytopenia (6.5%), diarrhea (6.5%), anorexia (6.5%), and vomiting (3.2%). CONCLUSION: Compared to FX, mFX may result in fewer Grade 3 or 4 non-hematological AEs, with a comparable response rate. However, further efforts might be required to reduce hematological AEs.

Prospective randomized study of endoscopic biliary stone extraction using either a basket or a balloon catheter: the BasketBall study.

BACKGROUND: In Japan and Europe, a retrieval basket is generally used for endoscopic extraction of bile duct stones, while in the US, a retrieval balloon is mainly used. However, the efficacies of these two devices have not been previously compared. Therefore, the present multicenter, prospective, randomized study was performed to compare the efficacies of these two devices for endoscopic biliary stone extraction. METHODS: This study was designed as a non-inferiority study in comparing a basket removal with a balloon removal. Six Japanese institutions participated in this study, which included 184 patients with bile duct stones <11 mm in diameter with no limitation in the number of stones. The stones were identified and measured during ERCP, after which the patients were randomly assigned to undergo endoscopic stone extraction using either a basket catheter or a balloon catheter. The primary end point was the rate of complete removals of stones within 10 min, and the secondary end point was the rate of procedure-related complications. RESULTS: There were 91 patients in the basket group and 93 in the balloon group. The rate of successful stone extraction within 10 min was 81.3 % (74/91) in the basket group and 83.9 % (78/93) in the balloon group (p = 0.7000). The complication rate was 6.6 % in the basket group and 11.8 % in the balloon group (p = 0.3092). Complications included bleeding, pancreatitis, and cholangitis. CONCLUSIONS: Basket and balloon catheters showed similar efficacies for endoscopic biliary stone extraction when stone size is 11 mm or smaller.

Stress chaperone mortalin regulates human melanogenesis.

In order to identify the cellular factors involved in human melanogenesis, we carried out shRNA-mediated loss-of-function screening in conjunction with induction of melanogenesis by 1-oleoyl-2-acetyl-glycerol (OAG) in human melanoma cells using biochemical and visual assays. Gene targets of the shRNAs (that caused loss of OAG-induced melanogenesis) and their pathways, as determined by bioinformatics, revealed involvement of proteins that regulate cell stress response, mitochondrial functions, proliferation, and apoptosis. We demonstrate, for the first time, that the mitochondrial stress chaperone mortalin is crucial for melanogenesis. Upregulation of mortalin was closely associated with melanogenesis in in vitro cell-based assays and clinical samples of keloids with hyperpigmentation. Furthermore, its knockdown resulted in compromised melanogenesis. The data proposed mortalin as an important protein that may be targeted to manipulate pigmentation for cosmetic and related disease therapeutics.

Significance of Endoscopic Sphincterotomy Preceding Endoscopic Papillary Large Balloon Dilation in the Management of Bile Duct Stones.

BACKGROUND: Endoscopic papillary large balloon dilation (EPLBD) is safe and effective in management of common bile duct stones (CBDS). Endoscopic sphincterotomy (EST) prior to EPLBD has been performed as a standard procedure. However, the significance of EST prior to EPLBD has not been well studied yet. AIMS: To compare the clinical outcomes of EPLBD with and without EST to evaluate the significance of EST. METHODS: Between April 2010 and March 2015, a total of 82 patients with naïve papillae underwent EPLBD with or without EST for the management of CBDS. A retrospective analysis compared the efficacy and safety of EPLBD with and without EST. RESULTS: Basic patient characteristics were not significantly different between the groups that underwent EPLBD with EST (n = 27) and without EST (n = 55). Complete stone removal rates were similar between the groups (100 % in the EST group and 98 % in the non-EST group, p = 1.00). There was no significant difference in the median balloon size (13 mm in both groups, p = 0.445), rate of application of mechanical lithotripsy (26 vs. 35 % in the EST and non-EST groups, respectively, p = 0.463), or the median procedure time (38 vs. 34 min in the EST and non-EST groups, respectively, p = 0.682). The overall adverse event rates were not statistically different (4 vs. 7 % in the EST and non-EST groups, respectively, p = 1.00). Pancreatitis, cholangitis, and hemorrhage rates were also similar in both groups. CONCLUSIONS: EST prior to EPLBD may be unnecessary since this study did not demonstrate its benefits.

EUS-guided rendezvous for difficult biliary cannulation using a standardized algorithm: a multicenter prospective pilot study (with videos).

BACKGROUND AND AIMS: Biliary cannulation is necessary in therapeutic ERCP for biliary disorders. EUS-guided rendezvous (EUS-RV) can salvage failed cannulation. Our aim was to determine the safety and efficacy of EUS-RV by using a standardized algorithm with regard to the endoscope position in a prospective study. METHODS: EUS-RV was attempted after failed cannulation in 20 patients. In a standardized approach, extrahepatic bile duct (EHBD) cannulation was preferentially attempted from the second portion of the duodenum (D2) followed by additional approaches to the EHBD from the duodenal bulb (D1) or to the intrahepatic bile duct from the stomach, if necessary. A guidewire was placed in an antegrade fashion into the duodenum. After the guidewire was placed, the endoscope was exchanged for a duodenoscope to complete the cannulation. RESULTS: The bile duct was accessed from the D2 in 10 patients, but from the D1 in 5 patients and the stomach in 4 patients because of no dilation or tumor invasion at the distal EHBD. In the remaining patient, biliary puncture was not attempted due to the presence of collateral vessels. The guidewire was successfully manipulated in 80% of patients: 100% (10/10) with the D2 approach and 66.7% (6/9) with other approaches. The overall success rate was 80% (16/20). Failed EUS-RV was salvaged with a percutaneous approach in 2 patients, repeat ERCP in 1 patient, and conservative management in 1 patient. Minor adverse events occurred in 15% of patients (3/20). CONCLUSIONS: EUS-RV is a safe and effective salvage method. Using EUS-RV to approach the EHBD from the D2 may improve success rates.

A case of a teenage boy with eosinophilic gastroenteritis with esophageal involvement developing a hemorrhagic duodenal ulcer.

A boy in his early teens visited our hospital with chief complaints of hematemesis and tarry stools. Upper gastrointestinal endoscopy identified a hemorrhagic duodenal ulcer, for which hemostasis was performed using a clip. Proton pump inhibitor (PPI) administration diminished the ulcer but relapse occurred after PPI discontinuation. The esophagus showed concentric rings and longitudinal linear furrows considered to be characteristic of eosinophilic esophagitis. Biopsies of the duodenal ulcer and the esophagus revealed marked infiltration of eosinophils, leading to a diagnosis of eosinophilic gastroenteritis with esophageal involvement. Steroid treatment was initiated, and the duodenal ulcer and esophagitis resolved. Endoscopic findings characteristic of eosinophilic esophagitis were key to the diagnosis of eosinophilic gastroenteritis.

[A case report of pancreatic serous cystadenoma coexistent with adenosquamous carcinoma].

A 70-year-old man was admitted to our hospital because a mass was incidentally found in the body of the pancreas. The mass was suspected to be serous cystadenoma from the findings of abdominal enhanced computed tomography, magnetic resonance imaging and endoscopic ultrasonography. In addition, another solid mass was detected in the pancreatic head on imaging tests. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed stenosis both of the main pancreatic duct at the head and bile duct, but the brushing cytology of the bile duct at ERCP showed no malignant cells. However, the findings of several examinations strongly suggested the coexistence of a serous cystadenoma and a pancreatic cancer, therefore we conducted spleen-preserving total pancreatectomy, and the pathological findings of the resected specimen showed serous cystadenoma coexistence with pancreatic adenosquamous carcinoma.

Use of samples from endoscopic ultrasound-guided 19-gauge fine-needle aspiration in diagnosis of autoimmune pancreatitis.

BACKGROUND & AIMS: Histologic techniques are used to distinguish autoimmune pancreatitis (AIP) from pancreatic malignancies and to confirm the etiology of pancreatitis. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a well-established technique used in the diagnosis of pancreatic cancer. However, it is unclear whether specimens obtained from pancreatic lesions by EUS-FNA are adequate for the histologic diagnosis of AIP, because the evaluation of tissue architecture and immunostaining assays usually require larger samples. METHODS: We evaluated samples collected by EUS-FNA with a conventional 19-gauge needle by histologic analysis, looking for features of AIP. We analyzed data from 44 patients who were diagnosed with AIP and underwent EUS-FNA with a 19-gauge needle from January 2004 to September 2010. The FNA specimens were reviewed by histologic analysis; AIP was diagnosed based on the presence of lymphoplasmacytic sclerosing pancreatitis or immunoglobulin (Ig)G4-positive plasma cells in the infiltrate. RESULTS: The specimen amount was inadequate from 3 patients. Among the remaining 41 patients, histopathologic analysis revealed lymphoplasmacytic sclerosing pancreatitis in 17 samples and IgG4-positive plasma cells in 5 (3 samples were positive for both); no samples had granulocytic epithelial lesions. Therefore, 19 patients (43%) were diagnosed with AIP based on histologic analysis. One patient had temporary abdominal pain. CONCLUSIONS: EUS-FNA, with a 19-gauge needle, is a safe and reliable procedure for obtaining pancreatic samples for the histologic analysis of AIP. Although it does not have a high diagnostic yield, it might be useful in patients without typical features of AIP because it would allow patients to avoid surgery.

Expression of retinoid X receptor alpha is decreased in 3'-methyl-4-dimethylaminoazobenzene-induced hepatocellular carcinoma in rats.

The identification of the specific molecular targets, which underlie liver carcinogenesis is essential for the establishment of an effective strategy for the prevention and/or treatment of hepatocellular carcinomas (HCCs). We previously found that a malfunction of RXRalpha due to its aberrant phosphorylation was associated with the development of HCCs. However, it has remained unclear whether the abnormalities in the expression of RXRalpha or the other retinoid receptors play a role in the early stage of liver carcinogenesis. The present study was designed to determine whether alterations in the expression of RXRalpha and the other retinoid receptors RARalpha and RARbeta are involved in hepatocarcinogenesis using a 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB)-induced rat liver carcinogenesis model. We found that immunohistochemical expression of RXRalpha was decreased in liver cell tumors (HCCs and adenoma) and glutathione S-transferase placental form (GST-P)-positive foci, which is a precancerous lesion of HCC, when compared with the non-cancerous tissues. Western blot and RT-PCR analyses revealed a progressive decrease in the expression levels of RXRalpha, RARalpha, and RARbeta proteins and their mRNAs in 3'-MeDAB-induced HCCs and their surrounding tissues, when compared with the normal liver tissues from the control group. Moreover, the expression level of beta-catenin, the heterodimeric partner for both RXRalpha and RARalpha, was immunohistochemically observed in the cytoplasm and, in some cases, in the nucleus of HCC cells. The nuclear expression of cyclin D1, the downstream target molecule of beta-catenin, was also increased in HCC cells when compared with their adjacent normal appearing tissues. Our findings suggest that loss of retinoid receptors, especially RXRalpha, plays a critical role in the chemically-induced rat liver carcinogenesis and this might be associated with the activation of beta-catenin-related signaling pathway.

Late-onset neutropenia in patients treated with rituximab for non-Hodgkin's lymphoma.

Late-onset grade 4 neutropenia occurred in 3 (5.6%) of 54 non-Hodgkin's lymphoma patients treated with rituximab between September 2001 and March 2004. Neutropenia appeared 5 to 25 weeks after administration of cytotoxic agents in combination with rituximab and recurred 4 and 17 weeks after the first onset in 2 patients. Five episodes occurred in a total of 332 cycles of rituximab therapy. Bone marrow findings at the time of late-onset neutropenia showed neutrophil maturation arrest with or without reversible myeloid dysplasia in 3 episodes and selective depletion of the myeloid series in 1 episode. Neither circulating immune complexes nor antineutrophil antibodies were detected during the 3 episodes that we evaluated. Bone marrow cells stained CD8- and CD57-. Late-onset neutropenia resolved 5 to 7 days after granulocyte colony-stimulating factor therapy was started. Further studies are needed to determine how rituximab functions and to identify appropriate countermeasures.