Transmission dynamics variability of lineage 2 Mycobacterium tuberculosis strains in Kobe, Japan, determined using population-based whole-genome sequencing analysis.

Currently, tuberculosis (TB) in Japan is highly prevalent among elderly patients who were born during a time when TB was highly prevalent. Mycobacterium tuberculosis (Mtb) lineage 2 (L2) is the predominant strain in the country. Moreover, the proportion of foreign-born patients with TB has been increasing. This epidemiological situation in Japan motivated us to explore the heterogeneity in transmission dynamics among the sublineages of Mtb L2 within this aging population. For this purpose, we conducted a population-based whole genome sequencing analysis of 550 Mtb strains in Kobe, Japan, and employed pairwise single nucleotide polymorphism (SNP) distance clustering and terminal branch length (TBL) distribution analysis to assess Mtb transmission. The genomic clustering rate with a threshold of ≤5 SNPs was significantly lower in elderly patients aged 70 years or higher than in non-elderly patients. The elderly patient group showed significantly longer TBL than the non-elderly group. These results supported the notion that reactivation of distant infection is a major driving force for the high incidence of TB in elderly individuals. The age group distribution and frequency of lineages/sublineages were found to significantly differ between foreign-born and Japan-born patients. The increased proportion of foreign-born patients might have resulted in more strain diversity in Japan. The L2.2.A sublineage demonstrated a significant association with elderly patients and exhibited lower transmission rates, which indicate to be prone to reactivate from long-term latency. In contrast, L2.2.Modern, showed a strong association with younger and foreign-born patients. This sublineage showed a high genomic cluster rate, suggesting its high transmissibility. The other three major sublineages, namely L2.2.AA2, L2.2.AA3.1, and L2.2.AA3.2, exhibited a consistent increase in cluster rates across varying SNP thresholds, indicating their relatively recent emergence as endemic sublineages in Japan. In conclusion, this study highlights distinct differences in the transmission dynamics of L2 sublineages within an aging society.

Clinical outcomes of COVID-19 caused by the Alpha variant compared with one by wild type in Kobe, Japan. A multi-center nested case-control study.

OBJECTIVES: The emergence of the Alpha variant of novel coronavirus 2019 (SARS-CoV-2) is a concerning issue but their clinical implications have not been investigated fully. METHODS: We conducted a nested case-control study to compare severity and mortality caused by the Alpha variant (B.1.1.7) with the one caused by the wild type as a control from December 2020 to March 2021, using whole-genome sequencing. 28-day mortality and other clinically important outcomes were evaluated. RESULTS: Infections caused by the Alpha variant were associated with an increase in the use of oxygen (43.4% vs 26.3%. p = 0.017), high flow nasal cannula (21.2% vs 4.0%, p = 0.0007), mechanical ventilation (16.2% vs 6.1%, p = 0.049), ICU care (30.3% vs 14.1%, p = 0.01) and the length of hospital stay (17 vs 10 days, p = 0.031). More patients with the Alpha variant received medications such as dexamethasone. However, the duration of each modality did not differ between the 2 groups. Likewise, there was no difference in 28-day mortality between the 2 groups (12% vs 8%, p = 0.48), even after multiple sensitivity analyses, including propensity score analysis. CONCLUSION: The Alpha variant was associated with a severe form of COVID-19, compared with the non-Alpha wild type, but might not be associated with higher mortality.

[A Case of Severe Bradycardia Induced by Combination Chemotherapy with Cisplatin and 5-Fluorouracil].

A 78-year-old man with Stage III esophageal cancer was referred to our hospital. Combination chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5-FU) was initiated. The patient experienced bradycardia episodes after starting the cisplatin infusion on day 1; he was otherwise asymptomatic. Therefore, combination chemotherapy was continued. However, on day 4, his heart rate dropped to 22 beats/min, with no other symptoms; however, treatment was stopped. After treatment was stopped, the patient's heart rate improved gradually and returned to normal in a few days. Combination chemotherapy with CDDP and 5-FU is a useful treatment for esophageal cancer, but it may induce severe bradycardia. Therefore, we must perform infusion therapy with caution.

Paget's disease of the male breast: a case report.

The patient was a 91-year-old man with change in nipple appearance, itching and redness, and a palpable breast mass. At presentation, mammary Paget's disease (PD) was clinically suspected. Skin biopsy was performed and showed epidermis invaded by Paget cells, characterized by hyperchromatic nuclei and abundant pale-staining cytoplasm. Computed tomography and mammary ultrasonography confirmed the absence of an underlying invasive carcinoma, and the patient underwent right mastectomy and sentinel lymph node biopsy (SLNB). Both sentinel lymph nodes were found to be negative perioperatively, and further axillary dissection was not performed. Pathological results revealed no malignancy under the nipple, yet the Paget cells were more widely spread than expected. The patient was followed up without the need of postoperative chemotherapy. Male mammary PD is an extremely rare breast cancer, and there is no standard preoperative assessment or operative procedure. Mammography is many times unable to detect possible underlying breast carcinoma in female patients with mammary PD, and previous studies have reported that the detection rate was less than 50 %. However, some researchers reported that magnetic resonance imaging (MRI) might be more detectable to confirm the extent of the cancer. The extent of the skin change around the nipple is often different from the actual perimeter of Paget cells. In extra-mammary PD, mapping biopsy is known to be useful to determine areas free of cancer. The benefits of SLNB have also been demonstrated for the management of less invasive breast cancers, and previous reports have shown that the use of SLNB is reasonable for treatment of mammary PD without underlying invasive cancer. MRI, mapping biopsy, and SLNB are all less invasive procedures and thus may be suitable for treatment of male mammary PD.

Novel non-trocar technique for laparoscopic radiofrequency ablation.

We have developed a novel insertion method, a non-trocar technique (NTT), for laparoscopic radiofrequency ablation, whereby an ablation needle, guided by a 14.8-mm echo probe (PVM-787LA; Toshiba, Tokyo, Japan), accurately and easily punctures the target tumor in the liver. By existing methods, an ablation needle is inserted into the abdominal cavity through a puncture hole away from the echo probe because of the presence of a 15-mm trocar. Under such circumstances, fitting and sliding an ablation needle along the groove of the probe into the abdominal cavity is difficult because of the longitudinal dissociation between the needle and the probe. To avoid this dissociation, an echo probe is inserted directly through the small incision from which the 12-mm trocar is withdrawn and an ablation needle is introduced directly into the abdominal cavity through a puncture hole adjacent to and slid along the groove of the probe.

[A case report of intrahepatic cholangiocarcinoma diagnosed as lung cancer with liver metastasis treated with radiofrequency ablation].

In December 2008, a 43-year-old male who had been pointed out a nodular shadow in the right upper field on a chest radiography was admitted to hospital. A 35 mm mass infiltrating to superior vena cava in the right upper lobe of the lung, and 32 mm mass in the liver at S7 were detected by CT. Pathological diagnosis of the liver tumor was adenocarcinoma. Under the diagnosis of lung carcinoma and liver metastasis, systemic chemotherapy was started from January 2009. Radiofrequency ablation (RFA) therapy was added for liver S7 mass in February, and radiation therapy was performed for lung mass in December. The lung lesion has markedly reduced, but the liver lesion recurred in October 2009, which continued to grow up to 80 mm until August 2010. He presented to our hospital with the diagnosis of liver metastasis of controlled primary lung cancer. In October, we performed right hepatectomy with diaphragma and right lung resection. The pathological diagnosis was intrahepatic cholangiocarcinoma. Multiple recurrences in remnant liver, lung and peritoneal metastasis were detected in January 2011. For intrahepatic cholangiocarcinoma, hepatectomy is the only established treatment, and RFA treatment remains controversial. Clinical diagnosis of multiple cancers should be decided with caution.

[A case report of multiple advanced hepatocellular carcinomas treated by combination therapy with hepatectomy and particle therapy].

We report a case of multiple advanced hepatocellular carcinomas (HCC) with bilobar distribution treated by combination therapy of hepatectomy and particle therapy (carbon ion therapy). A 73-year-old man who had been pointed out hepatic tumors on abdominal CT was referred to our hospital in February 2010. Advanced HCCs; 8 cm Vp3 and 6 cm in the left lobe, 4 cm in the posterior segment, and 1 .5 cm in the S8 area, were detected by abdominal dynamic CT and EOB-MRI etc. Curative resection was not applied due to insufficiency of liver function and unfavorable anatomical tumor locations. Accordingly we have developed a novel combination therapy of hepatectomy and particle therapy. First we performed left lobectomy in March 2010, followed by administration of particle therapy to the posterior segment for local control in May. Then, transcatheter arterial chemoembolization was administered 4 times for residual tumors. The patient survives for 15 months after the initial therapy with good local control.

[Particle beam radiotherapy with a surgical spacer placement for unresectable sacral chordoma].

Sacral chordomas constitute more than half of all chordomas and have a slower local growth than other bone malignant tumors. Although complete radical resection produces a longer local control and disease-free survival at the initial visit, chordomas are already often too large for complete resection to be possible. Particle radiotherapy consisting of proton and carbon-ion is a promising new modality which has an inherent anti-tumor effect against many types of malignancies. However, the application of particle radiotherapy for tumors adjacent to the gastrointestinal tract like sacral chordoma is restricted because the tolerance dose of the intestine is extremely low. A novel two-step treatment was developed with surgical spacer placement and subsequent proton radiotherapy to administer particle radiotherapy with curative intent. This report presents a case of a patient with a huge sacral chordoma treated by this method. This new strategy may potentially be an innovative and standard therapy for unresectable sacral chordoma in the near future.

[A case of Vp4 portal vein tumor thrombosis--a complete remission achieved with dual treatment of surgery plus percutaneous isolated hepatic perfusion].

We herein report a case of advanced hepatocellular carcinoma (HCC) with Vp4 portal vein thrombosis (PVTT). All of the hepatic tumors have completely disappeared for more than two years by a dual treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP). A 68-year-old man was referred to our institution in May 2009. The abdominal CT scan demonstrated massive HCC in the right robe of the liver with PVTT reaching the portal trunk (Vp4). We semi-electively performed a right hepatectomy together with thrombectomy of the PVTT. Subsequently, we underwent a PIHP (doxorubicin 90 mg/m2). This resulted in normalization of serum AFP and PIVKA-II levels. Dual treatment is considered to be the strongest therapeutic modality for multiple advanced HCC with severe PVTT.

[A long-term survival case of postoperative lymph node metastases from hepatocellular carcinoma treated with lymph node dissection and percutaneous isolated hepatic perfusion (PIHP)].

We report a long-term survival case of hepatocellular carcinoma (HCC) with recurrence in the liver and multiple lymph nodes treated with lymph node dissection and percutaneous isolated hepatic perfusion (PIHP). The patient was a 70-year-old man with HCC. In 1999, transcatheter arterial chemoembolozation (TACE) was performed for HCCs. In 2000, partial hepatectomy was achieved for a recurrence in the liver. In 2002, CT scan disclosed multiple lymph node metastases around the hepatic artery and the recurrence in the liver. We performed a lymph node dissection and radio-frequency ablation for the hepatic tumor. After the operation, PIHP was performed for residual lymph node metastases. Then, a recurrence in the liver occurred 3 times, but was treated successfully with local therapy. The patient survives for 10 years after the initial therapy, and 8 years after a lymph node dissection.

Relative adrenal insufficiency manifested with multiple organ dysfunction in a liver transplant patient.

Relative adrenal insufficiency is now a well-known clinical condition that occurs in critically ill patients particularly with septic complication. However, this pathology has long been unrecognized until recently in liver transplantation patients, for whom postoperative immunosuppressive therapies almost always comprise corticosteroids. We report an obvious case of relative adrenal insufficiency manifested by severe multiple organ dysfunction in a recipient after living donor liver transplantation (LDLT). A 38-year-old woman with multiple hepatocellular carcinoma developed refractory liver failure 2 months after the completion of the dual treatment; namely a cytoreductive right hepatectomy for bulky main tumors followed by 2 courses of percutaneous isolated hepatic perfusion for residual tumors in the remnant liver. She underwent a right-lobe LDLT, and postoperative immunosuppression was initiated with a low-dose tacrolimus monotherapy without corticosteroid because of a severe septic condition before transplantation. Postoperatively, she developed progressive hyperbilirubinemia, renal dysfunction, and coagulopathy. As the corticotropin stimulation test suggested the relative adrenal insufficiency, corticosteroid was commenced 40 days after LDLT. Thereafter, multiple organ dysfunction resolved dramatically and promptly. The patient is presently alive and well with completely normalized liver function 45 months after LDLT.

[Sustained complete remission with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP) for bilobar multiple hepatocellular carcinoma with portal venous tumor thrombus--a case report].

For patients with multiple bilobar hepatocellular carcinoma (m-HCC) and/or advanced portal venous tumor thrombus (Vp3, 4), there has been no effective therapy, and the survival of more than 6 months was exceptional. Under these circumstances, we have developed a dual treatment (dual Tx) that combines reductive hepatectomy with percutaneous isolated hepatic perfusion (PIHP) for such patients. This dual Tx offers the high-rate of mid- and long-term survival in a subset of patients who had previously a dismal prognosis. Herein, we report a patient with Vp4 m-HCC who was successfully treated with dual Tx and survived for more than 2 years with a complete remission of hepatic tumors. A 53-year-old man had main tumors in the right lobe liver and multiple bilobar intrahepatic metastases (IM) with portal venous tumor thrombus reaching the portal trunk. He underwent an extended right hepatectomy with portal venous tumor thrombectomy, and subsequently PIHP twice in a 3-month period after reductive hepatectomy. After dual Tx, he had sustained complete remission for more than 2 years. He died because of obstruction of the superior vena cava by recurrent tumors in the mediastinum. His clinical course after treatment strongly indicates that the dual Tx should become a major treatment option for patients with Vp3, 4 m-HCC.

[A case of multiple hepatocellular carcinoma with rapidly progressing bilateral portal vein tumor thrombosis--a complete remission achieved with dual treatment of reductive surgery plus percutaneous isolated hepatic perfusion].

We herein report a case of multiple advanced hepatocellular carcinoma (HCC) with rapidly progressing portal vein tumor thrombosis (PVTT). All of the hepatic tumors have completely disappeared for more than two years by a dual treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP). A 55-year-old man was referred to our institution on June 30, 2003. The abdominal CT scan demonstrated multiple massive HCC in the entire liver with PVTT reaching the portal trunk (Vp4). Two weeks later, the PVTT rapidly progressed to the umbilical portion of the left portal vein, and to the confluence of the superior mesenteric vein and to the splenic vein. Thus, we semi electively performed an extended right hepatectomy together with thrombectomy of the PVTT. Subsequently, he underwent a repeated PIHP (1st; doxorubicin 90 mg/m2, 2nd doxorubicin 65 mg/m2). This treatment produced complete tumor clearance of all of the residual tumors in the left liver. In March 2005, he underwent partial pneumonectomy for a metastatic lung. This again resulted in normalization of serum AFP and PIVKA-II levels. Dual treatment is considered to be the strongest therapeutic modality for multiple advanced HCC with severe PVTT. In addition, a close follow-up is required because in such far advanced cases, metastatic lesions most likely recur in the liver but also in the distant organs.

Adenocarcinoma arising in a tubular duplication of the jejunum.

To our knowledge, only five cases of malignant changes in small-bowel duplication have been reported previously in the English-language literature, and these were found only in ileal duplications. We describe a unique case of adenocarcinoma arising in a tubular duplication of the jejunum; this is the oldest patients in whom malignant tumor of alimentary tract duplication has been reported. A 73-year-old man was admitted to our hospital because of lower abdominal pain. Computed tomography (CT) and ultrasonography showed two abdominal masses; one, about 5 cm in size, was observed in the upper abdomen, the superior mesenteric artery (SMA) and the other, which was a well-demarcated heterogeneous mass, was revealed in the lower abdomen. Laparotomy revealed the mass in the upper abdomen involved the SMA and transverse colon, while the mass in the lower abdomen was of white globular form, ping-pong ball size, in the jejunal serosa approximately 40 cm on the anal side from Treiz's ligament. Transverse colostomy and a partial jejunectomy were performed, and the tumor was resected. Histologically, the diagnosis was adenocarcinoma arising in a tubular duplication of the jejunum. The patient died of necrosis and perforation of the intestine due to obstruction of the SMA 7 months after the surgery. Autopsy revealed that the upper abdominal mass consisted of metastatic foci associated with the lymph node of the SMA.

Effect of portal vein embolization on function of the nonembolized lobes of the liver: Evaluation by first-pass hepatic lidocaine extraction in dogs.

BACKGROUND: Portal vein embolization (PVE) of hepatic lobes planned for resection is known to increase the margin of safety in extended hepatic resection. We examined whether volume gain could directly translate into functional gain in the nonembolized hepatic lobes after PVE, using a unique pharmacologic model of hepatic venous isolation and charcoal hemoperfusion. METHODS: Lidocaine hydrochloride (8 mg/kg) was infused over 10 minutes in the portal vein of beagles with hepatic venous isolation and charcoal hemoperfusion, which prevented hepatic recirculation of the drug, and the lidocaine first-pass hepatic extraction ratio (Lid-HER) was determined to assess the selective lobar function of the liver. First, the correlation between Lid-HER and hepatic parenchymal weight of the lidocaine perfusion area was studied. Second, PVE was performed of the left portal branch, and Lid-HER of the nonembolized lobes was determined 1 hour or 2 weeks after PVE. RESULTS: Hepatic venous isolation and charcoal hemoperfusion reduced (>95%) the postfilter and systemic lidocaine concentrations compared with prefilter concentrations. In the first study, a significant correlation was demonstrated between Lid-HER and hepatic parenchymal weight (P =.0023, r(2) = 0.992). In the second study, both weight ratio of the nonembolized lobes relative to the whole liver and Lid-HER of the nonembolized lobes showed significant increases 2 weeks after PVE of 1.7- and 1.9-fold, respectively. CONCLUSIONS: Hepatic-weight increase paralleled functional increase, as determined by Lid-HER, in the nonembolized hepatic lobes 2 weeks after PVE. Thus, volume change directly translated into functional change in future remnant noncirrhotic liver after PVE.