Necrotising fasciitis with extensive necrosis caused by Lactobacillus: a case report.

BACKGROUND: Necrotising fasciitis (NF) is a life-threatening soft-tissue infection that rapidly destroys the epidermis, subcutaneous tissue, and fascia. Despite their low virulence, Lactobacillus spp. can cause NF, and because of its rare incidence, there is limited information about its molecular and clinicopathological characteristics. We report a rare case of NF in a patient with type 2 diabetes mellitus diagnosed on admission and severe obesity due to infection with two types of Lactobacillus spp. that manifested in extensive necrosis. CASE PRESENTATION: A 48-year-old woman was referred to our hospital with a complaint of difficulty walking due to severe bilateral thigh pain. She presented with mild erythema, swelling, and severe skin pain extending from the pubic region to the groin. The patient was morbidly obese, had renal dysfunction, and had diabetes mellitus diagnosed on admission.; her LRINEC (Laboratory Risk Indicator for Necrotising Fasciitis) score was 9, indicating a high risk of NF. An exploratory surgical incision was made, and NF was diagnosed based on fascial necrosis. Emergent surgical debridement was performed, and cultures of the tissue culture and aspirated fluid/pus revealed two types of Lactobacillus spp.: Lactobacillus salivarius and L. iners. The patient was admitted to the intensive care unit (ICU), where antibiotics were administered and respiratory and circulatory management was performed. Diabetic ketoacidosis was detected, which was treated by controlling the blood glucose level stringently via intravenous insulin infusion. The patient underwent a second debridement on day 11 and a skin suture and skin grafting on day 36. The patient progressed well, was transferred from the ICU to the general ward on day 41, and was discharged unassisted on day 73. CONCLUSIONS: Lactobacillus spp. are rarely pathogenic to healthy individuals and can scarcely trigger NF. However, these bacteria can cause rare infections such as NF in immunocompromised individuals, such as those with diabetes and obesity, and an early diagnosis of NF is imperative; surgical intervention may be required for the prevention of extensive necrosis. The LRINEC score may be useful for the early diagnosis of NF, even for less pathogenic bacteria such as Lactobacillus.

Recent insights on the clinical, pathological, and molecular features of intraductal carcinoma of the prostate.

Intraductal carcinoma of the prostate, a unique histopathologic entity that is often observed (especially in advanced prostate cancer), is characterized by the proliferation of malignant cells within normal acini or ducts surrounded by a basement membrane. Intraductal carcinoma of the prostate is almost invariably associated with an adjacent high-grade carcinoma and is occasionally observed as an isolated subtype. Intraductal carcinoma of the prostate has been demonstrated to be an independent poor prognostic factor for all stages of cancer, whether localized, de novo metastatic, or castration-resistant. It also has a characteristic genetic profile, including high genomic instability. Recognizing and differentiating it from other pathologies is therefore important in patient management, and morphological diagnostic criteria for intraductal carcinoma of the prostate have been established. This review summarizes and outlines the clinical and pathological features, differential diagnosis, molecular aspects, and management of intraductal carcinoma of the prostate, as described in previous studies. We also present a discussion and future perspectives regarding intraductal carcinoma of the prostate.

Efficacy of the Addition of Robot-assisted Radical Cystectomy with Extracorporeal Urinary Diversion after an Enhanced Recovery Protocol.

PURPOSE: It is unclear if robotic radical cystectomy with extracorporeal urinary diversion (eRARC) provides additional benefit when performed along with enhanced recovery after surgery (ERAS). We assessed the additional efficacy of eRARC in terms of perioperative outcomes. MATERIALS AND METHODS: We retrospectively assessed 143 patients undergoing radical cystectomy with urinary diversion between June 2010 and December 2021 at a single center. The patients were assigned to three groups: open radical cystectomy (ORC) with conventional recovery after surgery (CRAS) [Group A], ORC with ERAS [Group B], and eRARC with ERAS [Group C]. A propensity score-matched analysis was performed to evaluate how ERAS and eRARC affected outcomes respectively. Meanwhile, multivariable analysis was used to detect the predictors of prolonged length of hospital stay (LOS). RESULTS: The median LOS was shorter after ERAS and eRARC. In the propensity score-matched analysis, ERAS was linked to a significantly shorter median LOS (28.0 vs. 20.0 days, P < .001), but eRARC was not associated with a shorter LOS (19.0 vs. 17.5 days, P = .21). Neither ERAS nor eRARC were connected with a reduce in complication rate. Following multivariable analysis, ERAS was found to be independently associated with shorter LOS (OR=0.23, P < .001), but eRARC demonstrated no such correlation (OR=0.29, P = .096). CONCLUSION: ERAS had strong association with shorter LOS, although eRARC did not contribute to additional efficacy. Neither ERAS nor eRARC decreased the complication rate.

Early restricted oxygen therapy after resuscitation from cardiac arrest (ER-OXYTRAC): protocol for a stepped-wedge cluster randomised controlled trial.

INTRODUCTION: Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%-95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS. METHODS AND ANALYSIS: ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%-95% of the target SpO2) or the control (98%-100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1-2 at 90 days after ROSC, to be compared using an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000046914).

Impact of Histological Variants on Clinical Responses to Pembrolizumab in Patients With Metastatic Urothelial Cancer.

BACKGROUND: The efficacy of anti-programmed celldeath protein 1 treatment in patients with urothelial carcinoma (UC) with molecular subtypes of histological variants has not been investigated. This study aimed to examine the impact of histological variants classified according to molecular subtypes on clinical outcomes in patients with platinum-resistant metastatic UC treated with pembrolizumab. PATIENTS AND METHODS: Data of 168 patients with metastatic UC who received intravenous pembrolizumab after platinum-based chemotherapy between December 2017 and November 2020 were retrospectively reviewed. Relationships between histological variant type (basal or luminal molecular subtypes) and survival outcome and response to immunotherapy were examined. Clinicopathological factors were analyzed using the Cox proportional hazards model. RESULTS: UC with histological variants was identified in 19 (11.3%) cases (basal subtype in 12; luminal subtype in 7). The median age of the patients was 72.5 years (range=40-89 years). The performance status was 0-1 in 151 (89.9%) patients. Liver metastasis was detected in 44 (26.2%) patients. The median progression-free survival was 3.5 months (range=0.5-34.3 months). Treatment with immune checkpoint inhibitors resulted in an overall mean survival (from the start of treatment) of 8.1 months (range=1.2-34.3 months). Patients with basal-type UC had significantly shorter progression-free survival and cancer-specific survival than those with pure UC (p=0.010 and p=0.035, respectively). A complete response was observed in eight patients (seven with pure UC, one with basal type). CONCLUSION: The basal histological variant might be a potential prognostic indicator in patients with platinum-resistant metastatic UC treated with pembrolizumab.

Relationship between the number of lymph nodes dissected and prognosis in muscle-invasive bladder cancer in the era of neoadjuvant chemotherapy.

OBJECTIVES: Many studies have shown a good prognostic association with a large number of lymph node dissections. However, most of these studies did not include patients who have received neoadjuvant chemotherapy. The purpose of this study was to verify the relationship between survival outcomes and the number of lymph nodes removed during radical cystectomy in patients with muscle-invasive bladder cancer in the era of neoadjuvant chemotherapy. METHODS: This retrospective study considered patients who were diagnosed with clinical ≥T2N0M0 muscle-invasive bladder cancer and treated with radical cystectomy at the Nagoya University Hospital and affiliated hospitals from January 2004 to December 2019. We excluded patients who had a history of upper tract urothelial cancer or non-urothelial carcinoma. The association between prognosis and the number of lymph nodes removed was investigated. RESULTS: We retrospectively enrolled a total of 477 patients. The mean number of lymph nodes dissected was 14. Two hundred and twenty-six patients (47.4%) received neoadjuvant chemotherapy. More extensive lymphadenectomy (≥15 lymph nodes) correlated with better 5-year overall survival across all patients (68% vs. 57%, p = 0.01). In patients who received neoadjuvant chemotherapy, there was no difference in overall survival according to the number of dissected lymph nodes (66% vs. 71%, p = 0.433). In patients who did not receive neoadjuvant chemotherapy, ≥15 lymph nodes dissected was associated with significantly better overall survival (70.3% vs. 46.9%, p < 0.01). CONCLUSIONS: No association between more aggressive lymph node dissection and prognosis was found in patients who underwent neoadjuvant chemotherapy. Conversely, extended lymph node dissection is desirable for patients who have not received neoadjuvant chemotherapy.

The Principles of Revised Clinical Guidelines about Palliative Sedation Therapy of the Japanese Society for Palliative Medicine.

Background: When the suffering of a terminally ill patient is intolerable and refractory, sedatives are sometimes used for symptom relief. Objective: To describe the main principles of revised Japanese clinical guidelines about palliative sedation therapy. Design: Consensus methods using the Delphi technique were used. Results: The main principles of the guidelines that were newly defined or developed are as follows: (1) palliative sedation was defined as "administration of sedatives for the purpose of alleviating refractory suffering" (excluding the aim of reducing patient consciousness); (2) palliative sedation was classified according to the method of administration of sedatives: respite sedation versus continuous sedation (including (continuous) proportional sedation and continuous deep sedation); (3) a description of state-of-the-art recommended treatments for difficult symptoms such as delirium, dyspnea, and pain before the symptom was determined as refractory was included; (4) the principle of proportionality was newly defined from an ethical point of view; and (5) families' consent was regarded as being desirable (mandatory in the previous version). Conclusions: We described the main principles of revised Japanese clinical guidelines about palliative sedation therapy. Further consensus building is necessary.

[ADOPTION OF ENHANCED RECOVERY AFTER SURGERY (ERAS) PROTOCOL FOR THE MANAGEMENT OF PATIENTS UNDERGOING RADICAL CYSTECTOMY IN JAPAN].

(Objectives) The Enhanced Recovery After Surgery (ERAS) protocols are standardized and multimodal perioperative care pathways designed to improve surgical outcomes by minimizing stress response and inflammation following surgery. First adopted in colorectal surgery, ERAS is now being employed in various other types of surgeries, most recently in patients undergoing radical cystectomy (RC). Implementation of ERAS protocols resulted in reductions in perioperative complication rates and length of hospital stay (LOS). However, information on the adoption of ERAS in patients undergoing RC in Japan is limited. The objective of this study was to evaluate the safety and efficacy of ERAS implemented in the Toyohashi Municipal Hospital in 2017 for the management of patients with RC. (Patients and methods) This was a retrospective study of 103 patients who underwent RC and urinary diversion from January 2012 to March 2019. Of the 103 patients, 71 underwent surgery prior to the introduction of the ERAS were allocated to the 'traditional' group, while 32 were exposed to the ERAS protocol were allocated to the 'ERAS' group. In this study, ERAS included no bowel preparation, preoperative carbohydrate loading, preoperative fluid reduction, preoperative fasting, reduced drainage use, no nasogastric intubation, and early postoperative drinking and eating. A comparative analysis was performed to evaluate LOS and postoperative complication rate (Clavien classification ≥2) after RC between the 'traditional' and 'ERAS' groups. (Results) Patient characteristics and intraoperative variables such as median age, sex, body mass index, clinical and pathological cancer stage, amount of bleeding, need for transfusion, and technique of urinary diversion did not differ between groups. However, duration of surgery was significantly shorter in the ERAS group than in the traditional group (402 min vs. 470 min; P = 0.03). Further, rate of complication was significantly lower (43.8% vs. 67.6%; P=0.03) and LOS after RC was significantly shorter (21 days vs. 28 days; P<0.001) in the ERAS group compared to the traditional group. Moreover, ERAS was an independent factor affecting shorter LOS after RC (OR, 5.22; 95% CI, 1.52-17.90; P = 0.009) in multivariate analyses. (Conclusions) It is possible that the ERAS protocol adopted in this study reduced the LOS and postoperative complication rate after RC at this site in Japan.

Efficacy of zoledronic acid in older prostate cancer patients undergoing androgen deprivation therapy.

OBJECTIVES: The purpose of this study is to evaluate the efficacy of annual zoledronic acid treatment in Japanese patients with nonmetastatic prostate cancer during androgen deprivation therapy (ADT). METHODS: This is a single institution 12-month study. Between 2016 and 2019, patients aged 70 years or older on ADT for nonmetastatic prostate cancer had bone mineral density (BMD) measured and 10-year probability of fracture calculated using fracture risk assessment tool (FRAX). Patients who showed osteopenia or had a 10-year hip fracture risk ≥ 3% or a 10-year probability of major osteoporotic fracture ≥ 20% were offered treatment with zoledronic acid 5 mg intravenously (ZA group). The patients who did not receive treatment were set as the control group. Lumbar and hip BMD were measured 6 and 12 months after treatment in the ZA group and 12 months after baseline in the control group. The yearly BMD change of both groups was compared. RESULTS: The mean ages of the ZA group (n = 26) and control group (n = 12) were 80.5 ± 9.1 and 76.1 ± 6.7 years, respectively. In the ZA group, lumbar and hip BMD changes at 12 months were +2.1% and +0.8%, respectively. In the control group, lumbar and hip BMD changes were -0.9% and -4.9%, respectively. There were statistically significant differences between the 2 groups in BMD percent changes (P < 0.05). CONCLUSIONS: Without intervention, BMD tends to continue to decrease during ADT. Our findings suggest that administration of zoledronic acid enables maintenance of BMD in the older adults.

[A CASE OF RENAL UNDIFFERENTIATED/UNCLASSIFIED SARCOMA WITH LONG-TERM SURVIVAL AFTER PRIMARY AND METASTATIC LESIONS].

(Case) A 56-year-old woman who complained of urinary frequency and macrohematuria. Abdominal US, enhanced CT and MRI revealed a left renal tumor. A left radical nephrectomy was performed in May 1997, and the pathological diagnosis was renal fibrosarcoma. Follow-up computed CT was performed routinely. A metastatic lesion in the right lung revealed 19 months after the nephrectomy.She underwent partial pneumonectomy in January 1999, and the pathological diagnosis was also fibrosarcoma. She was followed up until 2009 without recurrence.In 2015, she was admitted in the Department of Orthopedics due to femoral neck fracture in 2015, thus we could find out she was alive, tumor-free 18 years after the nephrectomy. We added the immunohistochemistical study to her specimen of kidney and lung, and the diagnosis was changed to undifferentiated/unclassified sarcoma. (Conclusion) Metastatic renal sarcoma has a poor prognosis in general. We experienced a long-term survival case of undifferentiated/unclassified renal sarcoma with lung metastasis, and report it with some literature review.

[POSTOPERATIVE CHRONIC PAIN FOLLOWING MESH AND NON-MESH REPAIR OF PELPIC ORGAN PROLAPSE].

(Objective) A FDA alert in 2011 warned about postoperative chronic pain following transvaginal mesh (TVM) for pelvic organ prolapse (POP). We studied cases with chronic pain after TVM, natural tissue repair (NTR) and laparoscopic salcocopopexy (LSC). (Methods) We retrospectively reviewed medical charts of patients who underwent POP operations in our hospital or were referred to us after POP operations in other hospitals between 2006 and 2016. Postoperative chronic pain was defined as persistent pain for more than three months following the first three months from the time of POP operations.Patients' characteristics and treatments were analyzed. (Results) In patients who underwent POP operations in our hospital, the rates of chronic postoperative pain after TVM, NTR and LSC were 12/2,457 (0.49%), 1/402 (0.26%) and 0/29 (0%), respectively. Another 8 patients were referred to us after POP operations in other hospitals. Thus, a total of 21 patients (15: TVM, 6: NTR) had either medications, surgical treatment or were referred to other doctors due to postoperative chronic pain. All of them were parous women aged 53 to 81 years old. Preoperative chronic pelvic pain was found in seven patients (33%), and another four patients (19%) had orthopedic diseases with chronic pain. The main locations of pain were; vagina 11, vulva 2, urinary bladder 2, urethra 1, coccyx 1, buttocks 1, anus 1, perineum 1 and groin 1. Nineteen patients had pharmacological treatment using tricyclic antidepressants, Ca2+ channel α2δ ligand and/or serotonin-noradrenalin reuptake inhibitor (SNRI); 9 (47%) of the patients showed a notable improvement. Three patients following TVM had surgical treatment; one with bladder mesh exposure was resolved with TURis, one with vaginal mesh exposure was resolved with mesh trimming, but one with tenderness on the mesh arm did not improve after a partial mesh removal. Four patients were referred to pain clinics. (Conclusions) Postoperative chronic pain can occur following both TVM and NTR therefore, attentive listening and proper medication are important as initial therapies. It is mandatory to examine the presence of mesh exposure in patients after using mesh. We should be careful about preoperative chronic pain, pelvic or elsewhere, as a risk factor for postoperative chronic pain.

[ABDOMINAL MASS AND ASCITES AS RISK FACTORS OF PELVIC ORGAN PROLAPSE].

(Objective) A rise of intra-abdominal pressure may exacerbate pelvic organ prolapse (POP) as well as abdominal hernias. This paper aims to assess the possible risk factors of an abdominal mass and ascites as comorbidities of POP. (Methods) We retrospectively reviewed the medical charts of 2,748 POP patients between 2010 and 2016 and extracted eight cases (0.3%) with abdominal mass and ascites as risk factors. (Results) All eight patients were multiparous women aged between 52 and 88 years old. Three patients (cases 1-3) were referred to us for surgery related to POP from gynecologists with previously undetected ovarian tumors. In case 1, we noticed abdominal distension during a transvaginal mesh (TVM) operation. Postoperative CT and MRI scans confirmed the presence of an ovarian tumor 24 cm in diameter (mucinous cystic tumor, borderline malignant). In case 2, transvaginal ultrasound could not detect the ovaries, but a transabdominal ultrasound, which was done to investigate urinary retention, revealed an ovarian tumor 18 cm in diameter (mucinous cystic adenoma). In case 3, a detailed patient history outlined the patient's sense of abdominal fullness and a transvaginal ultrasound found ovarian cancer 10 cm in diameter with ascites (serous adenocarcinoma). Case 4 suffered from autosomal dominant polycystic kidney disease (ADPKD) with large liver cysts. The patient underwent a TVM operation to treat the presenting POP with unusual bleeding (460 g). Case 5 had abdominal distension and cystocele due to huge abdominal mass (recurrence of malignant lymphoma); she desired conservative follow-up to tumor and POP due to old age (88 years old). Two patients suffered from end-stage cancer (case 6: colorectal cancer, case 7: breast cancer) with liver metastasis. In cases 6 and 7, the patients' POP worsened with the increase of ascites, which was managed conservatively. Case 8 presented with liver cirrhosis related ascites and a total uterine prolapse, simultaneously. Colpocleisis was cancelled due to the onset of hepatic coma. (Conclusions) Abdominal mass and ascites are risk factors of POP by increasing abdominal pressure and lesions such as ovarian tumors may present as POP. Even when POP patients are referred from gynecologists, a vaginal examination, carefully recorded patient history, and abdominal palpation should be included as part of a standard treatment regimen to reliably exclude underlying diseases.

Adding items that assess changes in activities of daily living does not improve the predictive accuracy of the Palliative Prognostic Index.

BACKGROUND: Changes in activities of daily living in cancer patients may predict their survival. The Palliative Prognostic Index is a useful tool to evaluate cancer patients, and adding an item about activities of daily living changes might improve its predictive value. AIM: To clarify whether adding an item about activities of daily living changes improves the accuracy of Palliative Prognostic Index. DESIGN: Multicenter prospective cohort study. SETTING: A total of 58 palliative care services in Japan. PARTICIPANTS: Patients aged >20 years diagnosed with locally extensive or metastatic cancer (including hematological neoplasms) who had been admitted to palliative care units, were receiving care by hospital-based palliative care teams, or were receiving home-based palliative care. Palliative care physicians recorded clinical variables at the first assessment and followed up patients 6 months later. RESULTS: A total of 2425 subjects were recruited and 2343 of these had analyzable data. The C-statistic of the original Palliative Prognostic Index was 0.801, and those of modified Palliative Prognostic Indices ranged from 0.793 to 0.805 at 3 weeks. For 6-week survival predictions, the C-statistic of the original Palliative Prognostic Index was 0.802, and those of modified Palliative Prognostic Indices ranged from 0.791 to 0.799. The weighted kappa of the original Palliative Prognostic Index was 0.510, and those of modified Palliative Prognostic Indices ranged from 0.484 to 0.508. CONCLUSION: Adding items about activities of daily living changes to the Palliative Prognostic Index did not improve prognostic value in advanced cancer patients.

[A CASE OF SUCCESSFUL MANAGEMENT BY LH-RH AGONIST FOR VESICOUTERINE FISTULA AFTER CESAREAN SECTION].

(Case) A 31-year-old woman noticed lower abdominal pain and urinary incontinence after voiding one month after third cesarean section. Cystoscopy and cystourethrography demonstrated a vesicouterine fistula at the posterior wall of the bladder. She complained of paroxysmal lower abdominal pain and slight incontinence without urge after voiding several times a month, which presented before and after menorrhea. Breast-feeding was ended 1 year after the labor, and then she underwent LH-RH agonist to keep amenorrhea. Urinary incontinence resolved completely within five months of hormonal therapy. During 8 years' follow-up, she remains asymptomatic and cystourethrography did not demonstrate the leakage. (Discussion) Most cases of vesicouterine fistula have been managed by surgical repair. As the pathophysiology of this disease resembles endometriosis, less-invasive hormonal therapy using LH-RH agonist can be a good treatment option before surgery.

Validation of the Simplified Palliative Prognostic Index Using a Single Item From the Communication Capacity Scale.

CONTEXT: Although the Palliative Prognostic Index (PPI) is a reliable and validated tool to predict the survival of terminally ill cancer patients, all clinicians cannot always precisely diagnose delirium. OBJECTIVES: The primary aim of this study was to examine the predictive value of a simplified PPI. In the simplified PPI, a single item from the Communication Capacity Scale was substituted for the delirium item of the original. METHODS: This multicenter prospective cohort study was conducted in Japan from September 2012 through April 2014 and involved 16 palliative care units, 19 hospital-based palliative care teams, and 23 home-based palliative care services. Palliative care physicians recorded clinical variables at the first assessment and followed up patients six months later. RESULTS: A total of 2425 subjects were recruited; 2343 had analyzable data. The C-statistics of the original and simplified PPIs were 0.801 and 0.800 for three week and 0.800 and 0.781 for six-week survival predictions, respectively. The sensitivity and specificity for survival predictions using the simplified PPI were 72.9% and 67.6% (for three week) and 80.3% and 61.8% (for six week), respectively. CONCLUSION: The simplified PPI showed essentially the same predictive value as the original PPI and is an alternative when clinicians have difficulties in diagnosing delirium.

Anaplastic large cell lymphoma in leukemic presentation: a case report and a review of the literature.

It is extremely rare that a patient with anaplastic large cell lymphoma (ALCL) demonstrates circulating lymphoma cells. A 10-year-old Japanese boy was presented with high-grade fever and cough. The physical examination revealed marked hepatosplenomegaly with ascites and lymphadenopathy in the cervical and periauricular areas. The white cell count was 26.2x10(9)/L with 95% of abnormal lymphoid cells, which were small to medium-sized with a high nucleus/cytoplasm ratio, basophilic cytoplasm, condensed nuclear chromatins, and 1 or 2 distinct nucleoli, hemoglobin 6.4 g/dL, and platelet 0.9x10(9)/L. A flow cytometric analysis of abnormal cells in both the peripheral blood and bone marrow samples was strongly positive for CD30 on their cell membranes. Karyogram and fluorescent in situ hybridization showed abnormal cells to have a characteristic chromosomal translocation, t(2;5)(p23;q35). Reverse transcriptase-polymerase chain reaction of peripheral blood cell-derived mRNA also indicated the fusion gene product of anaplastic lymphoma kinase and nucleophosmin. Subsequently, the patient was diagnosed to have ALCL with a rare clinical feature of a peripheral leukemic presentation, and his disease revealed to be refractory to chemotherapy. On the basis of the 11 childhood cases of ALCL with leukemic presentation so far published and reviewed herein, the prognosis is very poor.

Primary Ewing's sarcoma family tumors of the lung a case report and review of the literature.

Ewing's sarcoma family tumors (ESFT) have been reported to originate in a variety of sites, most commonly in the extremities. We herein report a case of a primary ESFT of the lung presenting in an 8-year-old boy. A histological examination of hematoxylin-eosin stained sections showed a homogeneous population of closely packed small neoplastic cells. The tumor cells were strongly positive for CD99/MIC2 and negative for the leukocyte common antigen, myoglobin, desmin, epithelial membrane antigen, AE1/AE3 and synaptophysin. The patient was treated with neoadjuvant chemotherapy and surgery. Nine months later, he is in good condition and chest CT scans have revealed no evidence of either local recurrence or distant metastasis. Cases of ESFT of the lung have been reported in recent years but there are still few reports of primary ESFT of the lung. To date, only eight cases of ESFT of the lung have been reported in the literature. This is the first report of an ESFT of the lung occurring in a patient under 10 years of age. The clinical course and therapeutic management of ESFT are also discussed.

Bone marrow transplantation in children with severe aplastic anemia using a conditioning regimen containing 3 Gy of total body irradiation, cyclophosphamide with or without antithymocyte globulin.

We have employed the 3 Gy total body irradiation (TBI) containing conditioning regimen to bone marrow transplantation (BMT) for severe aplastic anemia (SAA) in pediatric patients irrespective of donor type since March 1986. The outcome of BMT for 17 SAA patients is favorable. Eight patients received BMT from human leukocyte antigen matched-related donors (MRD) and nine received BMT from alternative donors. The conditioning regimen consisted of 3-Gy TBI and cyclophosphamide of 200 mg/kg in the BMT from MRD. In the case of BMT from alternative donor, antithymocyte globulin 10 mg/kg was added to the regimen. Fifteen of 17 patients (88%) engrafted on median of day 18 (range, 11-26) and all 13 evaluable patients showed complete donor chimerism by median 30 (range, 13-47) days after BMT. Fourteen patients have survived with a median follow-up of 67 (range, 2-228) months and the probability of survival was 81.9% (95% CI, 63.3-100%). No late complications including second malignancies caused by TBI have been observed and all three female patients have regular menstruation. In conclusion, TBI of 3 Gy appears to be an appropriate dose regarding to ensure engraftment and avoid the risk of late adverse event for SAA patients.

Infants with acute lymphoblastic leukemia and a germline MLL gene are highly curable with use of chemotherapy alone: results from the Japan Infant Leukemia Study Group.

Although infants with acute lymphoblastic leukemia (ALL) and a germline MLL gene have a better prognosis than comparable infants with a rearranged MLL gene, their optimal therapy is controversial. In 2 consecutive studies, conducted between 1996 and 2002, we treated 22 cases of infant ALL with germline MLL using chemotherapy alone. The 5-year event-free survival rate was 95.5% with a 95% confidence interval of 86.9 to 100%. All 21 infants with precursor B-cell ALL have been in first complete remission for 3.5 to 8.8 years. Most treatment-related toxicities were predictable and well tolerated, and neither secondary malignancies nor physical growth impairments have been observed. These results indicate that chemotherapy of the type described here is both safe and highly effective against infant precursor B-cell ALL with MLL in the germline configuration.