[A Case of Primary Anal Fistula Cancer with Extensive Intrapelvic Spreading That Was Successfully Treated with Bevacizumab plus mFOLFOX6].

The patient was a 68-year-old man who had an anal fistula for>10 years. He was referred to our institution after visiting a local physician with left femoral pain as the main complaint and received a diagnosis of high inflammatory response. We then found discharge of pus in the perianal region during a medical examination. We also found an extensive intrapelvic tumor during a computed tomography(CT)/magnetic resonance imaging examination. In addition, the level ofa tumor marker and inflammatory response were high. To control the inflammation, we performed seton drainage and sigmoid colostomy. On the basis of the pathological findings from the mucus component, we confirmed a diagnosis of fistula cancer. Considering that the progressive lesion had extensively spread, we decided to initiate chemotherapy alone because ofthe absence ofan indication for radiotherapy. We administered bevacizumab plus mFOLFOX6, and partial response was observed on a CT scan. We could control the progression ofthe disease for>6 months. The present case suggests that bevacizumab plus mFOLFOX6 can be an effective regimen for unresectable advanced fistula cancers.

Eculizumab in the treatment of atypical hemolytic uremic syndrome in an infant leads to cessation of peritoneal dialysis and improvement of severe hypertension.

BACKGROUND: Severe hypertension (HTN) and acute kidney injury frequently associated with atypical hemolytic uremic syndrome (aHUS) were refractory to various therapies in the pre-eculizumab era. Here we report the case of a 4-month-old boy who developed aHUS presenting with undetectable C3 protein, no predisposing mutations in complement factors, and no antibodies against factor H. METHODS: Repeated plasma infusions and nine sessions of plasmapheresis were ineffective. The patient initially required continuous hemodiafiltration and thereafter peritoneal dialysis. Despite vigorous antihypertensive treatment and improved fluid overload with dialysis, HTN persisted. His low C3 level (<20 mg/dl) suggested unrestricted complement activation. Therefore, based on the suspicion of unrestricted complement cascade in the pathogenesis, treatment with eculizumab, a human anti-C5 monoclonal antibody, was initiated with the aim of controlling disease activity. RESULTS: Eculizumab therapy resulted in the control of severe HTN and cessation of peritoneal dialysis. CONCLUSIONS: This infant with HTN and acute kidney injury associated with aHUS was treated successfully with eculizumab.

Effect of single-dose oral mizoribine pulse therapy twice per week for frequently relapsing steroid-dependent nephrotic syndrome.

AIM: To evaluate the efficacy of single-dose oral mizoribine (MZB) pulse therapy given twice weekly for frequently relapsing steroid-dependent nephrotic syndrome (FR-SDNS). METHODS: The subjects were 8 patients with FR-SDNS with a median age of 6.9 years old (range 3.1 - 18.0 y). The study was performed as a Phase II trial. The MZB dose was adjusted to achieve a peak blood level of 3 - 5 µg/ml (3.9 - 15.9 mg/kg/d, maximum dose: 750 mg) using a single dose given twice weekly before a meal. The therapeutic benefits of MZB pulse therapy were assessed based on a comparison of the incidence of relapse and the required daily dosage of prednisolone (PSL) in the 12 months prior to and following therapy. RESULTS: The incidence of relapse after therapy was significantly lower than that before therapy (2.5 ± 1.4 vs. 4.3 ± 0.5, p < 0.01) and the required daily dosage of prednisolone (PSL) after therapy was lower than that before therapy (0.48 ± 0.23 vs. 0.52 ± 0.32 mg/kg/d, not significant). However, this therapy was not effective for 3 out of 4 patients treated with cyclosporine. During follow-up, discontinuation of PSL was possible in 4 of 5 patients who showed a decreased rate of relapse after therapy. The peak blood concentration of MZB in these patients was significantly higher than that in 3 patients who did not show a decreased rate of relapse (3.95 ± 0.11 vs. 3.05 ± 0.21 µg/ml, p < 0.01). No adverse effects were observed in any patients. CONCLUSION: Our results show that single-dose oral MZB pulse therapy is effective in decreasing the frequency of relapse in some pediatric patients with FR-SDNS. A peak concentration of MZB of ~3.8 - 4.0 µg/ ml may be required for FR-SDNS therapy.

Severe COVID pneumonia and undetectable B cells after vaccination in patients previously treated with rituximab: a case series.

INTRODUCTION: The risk of developing severe COVID-19 illness despite completing vaccination for patients who have previously received immunosuppressive therapy is unclear. CASE PRESENTATION: We present three patients who received rituximab for treatment of autoimmune disorders who subsequently developed severe COVID-19 pneumonia post-vaccination requiring intensive care unit admission and found to have undetectable B cells. DISCUSSION: While there have been concerns about the effectiveness of COVID-19 vaccines in this patient cohort, this is the first case series to report development of severe COVID-19 illness after completing vaccination in those who previously received rituximab. Guidelines for the optimal timing of COVID-19 vaccination in relation to immunosuppressive therapy have been recently published, albeit after many patients in this subpopulation have already been vaccinated. CONCLUSION: This case series brings attention to the limited humoral response to vaccines in patients treated with rituximab, highlights existing guidelines and their limitations, and raises future considerations about the potential benefits to testing vaccine responsiveness.

Reduced Effective Oxygen Delivery and Ventilation with a Surgical Facemask Placed under Compared to over an Oxygen Mask: A Comparative Study.

OBJECTIVES: Consensus guidelines for perioperative anesthesia management during the COVID-19 pandemic recommend that patients wear a facemask in addition to their oxygen mask or nasal cannulae following tracheal extubation, where this is practical. The effects on effective oxygen delivery and ventilation of a surgical facemask under compared to over an oxygen (O2) mask are unclear. DESIGN: Single-center, comparative pilot study. Setting. Endoscopy procedure room at a major academic hospital. SUBJECTS: Five healthy anesthesiologists. Interventions. Using a carbon dioxide (CO2) sampling line positioned at the lips, the fraction of inspired O2 (FiO2), fraction of expiratory O2 (FeO2), expiratory end-tidal CO2 (EtCO2), and respiratory rate (RR) were measured under the following conditions: (1) a surgical facemask only, (2) a surgical facemask under an O2 mask, (3) an O2 mask only, and (4) a surgical facemask over an O2 mask. Measurements and Main Results. The sampled fractional expired oxygen (FeO2) at the lips was significantly lower when the surgical facemask was under compared to when over the O2 mask (27.9± 1.68 vs. 49.9 ± 6.27, p = 0.001), while there was no significant difference in inspired oxygen (FiO2). The sampled expiratory EtCO2 was significantly higher when the surgical facemask was under the O2 mask compared to when over the O2 mask (28.3 ± 8.5 vs. 23.5 ± 7.6, p = 0.026). The RR was not significantly different when the surgical facemask was under compared to over the O2 mask. CONCLUSIONS: Effective oxygen delivery and ventilation was reduced (lower FeO2 and increased EtCO2) when a surgical facemask was placed under compared to over an O2 mask.

Neonatal pertussis presenting as acute bronchiolitis: direct detection of the Bordetella pertussis genome using loop-mediated isothermal amplification.

We report a 28-day-old female infant with pertussis presenting as severe acute bronchiolitis with cyanosis. On admission, the patient's symptoms were similar to those of acute bronchiolitis. However, occasional apneic episodes with cyanosis and peripheral lymphocytosis suggested neonatal pertussis and prompted us to examine the presence of Bordetella pertussis using loop-mediated isothermal amplification (LAMP) based on the insertion sequence IS481. LAMP of the nasopharyngeal and intratracheal aspirates was positive for B. pertussis and a diagnosis of neonatal pertussis was made. As the clinical features of pertussis in neonates and early infancy are not characteristic, LAMP is a useful tool for rapid diagnosis of B. pertussis infection.

[Changes in the drug resistance of Haemophilus influenzae and Streptococcus pneumoniae isolated between 1997 and 2006].

We studied changes in the drug resistance of 606 strains of Haemophilus influenzae (H. influenzae) and 502 strains of Streptococcus pneumoniae (S. pneumoniae) isolated from our patients between 1997 and 2006. The incidence of beta-lactamase nonproducing ampicillin-susceptible H. influenzae (BLNAS) in 1997-1998 and 1999-2000 was 72.0 and 69.6%, respectively. In 2005-2006, the incidence of BLNAS decreased to 31.0%, while that of beta-lactamase nonproducing ampicillin-resistant H. influenzae (BLNAR) and intermediate-resistant H. influenzae increased to 65.5%. Remarkably early development of BLNAR and intermediate-resistant H. influenzae was found in patients younger than 3 years, as compared to patients older than 3 years. The proportion of penicillin-susceptible S. pneumoniae (PSSP) in 1999-2000 was 18.4%. In 2005-2006, the proportions of penicillin-resistant S. pneumoniae (PRSP) and penicillin-intermediate S. pneumoniae (PISP) were lower, while that of PSSP increased to 38.2%. An early increase in the proportion of PSSP was found in patients older than 3 years, as compared to patients younger than 3 years. The difference between age groups may be attributed to entrance into nursery school, frequent administration of antibiotics, and the immature immunological state of patients younger than 3 years. Therefore, changes in the drug resistance of H. influenzae and S. pneumoniae should be investigated separately, depending on the age of the patients. The minimum inhibitory concentrations of antibiotics, including cefditoren and cefcapene, against BLNAR and PRSP did not increase. The marked increase in intermediate-resistant H. influenzae and BLNAR mandates a re-evaluation of the directions for antibacterial agents.

[Huge ascending colon carcinoma, treated successfully with S-1 plus CPT-11, followed by significant tumor reduction and curative resection--a case report].

A 78-year-old woman was admitted to our hospital complaining of persistent abdominal pain and diarrhea. Computed tomography (CT) and colonoscopy (CF)revealed a huge ascending colon tumor, invading the descending part of the duodenum. The patient was treated preoperatively with a combination of S-1 plus CPT-11 (S-1 80 mg/body day 1-29, CPT- 11 100 mg/body day 1, 8, 15 and 22). No serious side effect was observed except low-grade fever and grade 2 appetite loss and diarrhea. Tumor reduction was significant on the preoperative CT and CF, with the invasion to the duodenum obscured. Right hemicolectomy with wedge resection of the duodenum was performed. Resected specimen revealed residual tumor in a small area of the submucosal to proper muscular layer of the contracted ascending colon, without pathological invasion to the duodenum. No nodal metastasis was observed. The patient was administered UFT (300 mg daily)postoperatively for two years and is still alive and free of disease after three years and ten months since the operation.

Clinical features and mutational survey of NPHS2 (podocin) in Japanese children with focal segmental glomerulosclerosis who underwent renal transplantation.

Recurrent FSGS is a major challenge in the field of nephrology. To clarify the role of NPHS2 defects in the pathogenesis of FSGS recurrence, we sequenced all eight exons of NPHS2 in 11 Japanese pediatric FSGS patients with or without post-transplant recurrence. All patients had biopsy-proven primary FSGS, had no family history of renal diseases or consanguinity, were steroid-resistant, and received living-related renal transplantation. The mean age at onset was 5.0 +/- 3.1 yr and mean age at renal transplantation was 10.4 +/- 4.1 yr. Mutational analysis of NPHS2 was performed using polymerase chain reaction and direct sequencing. We found a synonymous T/C polymorphism at alanine 318 (GCC to GCT) in seven of 11 patients but no other causative NPHS2 mutations. FSGS recurred immediately after transplant in seven patients, while the remaining four patients had no recurrence for 3.2-5.8 yr. There were no differences between recurrent and non-recurrent patients in the onset age and the interval from onset to ESRD. In conclusion, we detected no causative NPHS2 mutations in Japanese pediatric FSGS patients with or without post-transplant recurrence. Further studies on the involvement of other genes are required to better understand recurrent FSGS.

Enteral immuno-enhanced diets with arginine are safe and beneficial for patients early after esophageal cancer surgery.

We previously reported that provision of immediate enteral nutrition (EN) with a certain amount of omega (omega)-3 fatty acids (FAs) in patients after esophageal cancer surgery resulted in reduced platelet aggregation, coagulation activity, and cytokine production. We investigated whether EN using immuno-enhanced diet (IED) containing a large amount of omega-3 FAs as well as arginine and RNA affected the above-described responses. We also attempted to reveal whether arginine in the IED can potentially harm patients who undergo esophageal cancer surgery. Twenty-nine patients with esophageal cancer who underwent similar surgical procedures were selected. All patients received EN starting immediately after surgery. Fourteen patients received the formula with fewer omega-3 FAs, and fifteen patients received the IED. Administration of the IED tended to inhibit postoperative decrease in platelet count. Prothrombin activity and thrombin-antithrombin III complex levels were significantly reduced in the IED group. Plasma IL-8 levels were significantly lower (P < 0.05) in patients without the IED on the fifth postoperative day (POD). The proportion of T-cells was significantly higher (P < 0.05) in the IED group on PODs 1 and 7. Nitrate/nitrite levels did not differ significantly between the two groups. Early EN with an IED may enhance the inhibitory effects on postoperative platelet aggregation and hypercoagulation, and appeared to be advantageous to T-cell proliferation. These effects are expected to be beneficial in patients at risk of developing infectious complications. This study also showed that the IED could be safely used without any adverse effects for patients early after a radical surgery for the esophageal cancer.

Kidney transplantation in pediatric recipients with mental retardation: clinical results of a multicenter experience in Japan.

BACKGROUND: There are few published reports on kidney transplantation (KT) in physically handicapped patients with mental retardation. The aim of this study is to clearly identify the outcome of KT in these patients and clarify whether handicapped patients can be candidates for KT. METHODS: Our study identified 25 multiply handicapped transplant recipients from 8 institutions. Causes of mental retardation were chromosomal abnormality in 5 patients, genetic syndrome in 10 patients, developmental brain anomaly in 2 patients, and other or unknown causes in 8 patients. Primary diseases leading to end-stage renal disease were congenital urinary tract anomaly in 12 patients, focal segmental glomerulosclerosis in 3 patients, cystic kidney disease in 3 patients, and other in 7 patients. RESULTS: Twenty-three patients received living-related transplants from a parent and 2 patients received cadaver transplants. Twenty-two patients were on peritoneal dialysis therapy, 2 patients were on hemodialysis therapy at the time of KT, and 1 patient underwent preemptive KT. Eleven acute rejection episodes occurred in 8 patients. All episodes were completely reversed with treatments that included mainly methylprednisolone pulse therapy. Posttransplantation lymphoproliferative disorder occurred in 2 patients. Follow-up data showed that all grafts were functioning during a mean observation period of 41.1 months (range, 4 to 187 months). All persons providing primary support for patients were satisfied with the KT and believed that quality of life was improved in both transplant recipients and themselves. CONCLUSION: Results indicate that KT is not contraindicated in handicapped patients, but cannot determine which patients are unsuitable to undergo KT.

[A case of gastric cancer with peritoneal dissemination who achieved five-year survival by successive treatments with TS-1 alone and in combination with other drugs].

The patient was a 65-year-old male with gastric cancer. Peritoneal disseminations were detected during distal gastrectomy. CDDP and mitomycin C were administered into the peritoneal cavity. Administration of TS-1 was begun and continued without adverse effects. After 33 months, a high dose of CDDP was administered twice in combination with TS-1, because elevation of serum CEA levels and paraortic lymphnode swelling were observed for the first time. A partial response was obtained, but an elevation of CEA was seen again in three months. We then tried weekly administration of paclitaxel, and a complete response was achieved in three months. After three months'rest from chemotherapy, a third regrowth of the tumor was observed. Paclitaxel was ineffective, and so we opted for weekly administration of low-dose CDDP combined with TS-1, which led to the third recovery. Biweekly administration of CPT-11 combined with TS-1 followed the low-dose CDDP and was successfully continued five years after the surgery. The treatment course in this patient was fully suggestive for patients with advanced or recurrent gastric cancer because the use of newly available chemotherapeutic agents in turn was effective at each recurrence of the tumor and achieved five-year survival with minimal hospitalization.

[Two siblings with allergic purpura following Salmonella O9 enterocolitis].

Two siblings with allergic purpura after Salmonella O9 infection were reported. A girl (patient 1) aged 4 years and 4 months started to have knee joint pain and abdominal pain followed by purpura of the lower extremities and was referred to us for treatment of allergic purpura. She had contracted enterocolitis one month before visiting our hospital and Salmonella enteritidis was identified. During the course of the illness she had nephritis associated with allergic purpura. However, she made a favorable progress and proteinuria and hematuria disappeared within 6 months. A boy (an elder brother of patient 1) aged 6 years was admitted to our hospital because of the allergic purpura. He similarly had contracted Salmonella enterocolitis. He had severe gastro-intestinal symptoms including abdominal pain, vomiting and bloody stool, which rapidly subsided after initiation of treatment with intravenous hyperalimentation combined with prednisolone. It is possible that allergic purpura in our patients was closely associated with Salmonella enteritidis infection. Further accumulation of cases is a requisite to clarify an association of Salmonella enteritidis infection with allergic purpura and pathogenesis of allergic purpura.

[Influenza C virus isolated in Hiroshima Prefecture during the 1999/2000 winter season--a clinical and epidemiological study].

Influenza C virus (Inf. C) is one of pathogens of human respiratory tract infection and prevalent throughout the world at an early stage in life. However, Inf. C has been isolated only accidentally and there have been few reports on its clinical and epidemiological features. From November 1999 to March 2000, Inf. C was isolated from clinical specimens (throat swabs) of 4 pediataric patients with respiratory tract illness at Hiroshima Prefectural Hospital and was isolated in 4 peditaric patients at the other medical institutions in Hiroshima prefecture. There were no differences in clinical features including duration of illness, duration of fever, maximum body temperature between 4 patients with Inf. C infection and patients with influenza A (H1N1 and H3N2) and influenza B infection from 1992 to 2000. We investigated geographical distribution of patients with inf. C infection and analyzed for antigenic characteristics with a set of monoclonal antibodies against hemagglutinin-esterase glycoproteins. The data suggested that at least two antigenically different Inf. C prevalented in a region during winter from 1999 to 2000.

[The first report of an epidemic of human metapneumovirus infection in Japan: clinical and epidemiological study].

Human metapneumovirus (hMPV) was newly discovered as a pathogen in 2001 and is thought to be associated with respiratory disease. To elucidate the prevalence and clinical significance of hMPV among children, we investigated the positive cases of hMPV-RNA by reverse transcription-polymerase chain reaction (RT-PCR) in their nasopharyngeal specimens collected from January to August 2003 in Hiroshima Prefecture, Japan. Our prospective study revealed 77 hMPV-positive cases among 377 children with acute respiratory diseases. Clinical diagnoses of 77 hMPV-positive cases were as follows; bronchitis (33.8%), pneumonia (24.7%), acute respiratory illness (19.5%), asthmatic bronchitis (11.7%) and bronchiolitis (5.2%). The most common symptoms were cough (97.4%), high fever (94.8%) and rhinorrhea (76.6%). Most of the hMPV-positive cases were identified in the spring (between March and May), indicating the presence of an epidemic of hMPV infection in Hiroshima Prefecture. Phylogenetic analysis of the amplified F gene of hMPV isolates revealed that hMPV strains were divided into two genotypes and that their simultaneous circulation occurred within the same epidemic area of Hiroshima Prefecture.

A case of carbamoyl phosphate synthetase 1 deficiency presenting symptoms at one month of age.

Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is an autosomal recessive disorder of the urea cycle which causes hyperammonemia. Two forms of CPS1D are recognized: a lethal neonatal type and a less severe, delayed onset type. Neonatal CPS1D cases often present their symptoms within the first days of life. Delayed onset type were adolescents or adults, and infantile cases were rare. We report a case of CPS1D in a boy who developed symptoms at one month of age. He showed excellent response to treatments including continuous hemodialysis, drugs and a low-protein diet. His development and weight gain were good at the last follow-up at 1 year and three months of age. Molecular assay of the CPS1 gene demonstrated that the patient was heterozygous for c.2407C>G (R803G: maternal) in exon 20 and c.3784C>T (R1262X: paternal) in exon 32. Our clinical experience suggests that CPS1D could be one of the causes of hyperammonemia in early infantile cases.