[A Case of Liver Metastasis of Colorectal Cancer Successfully Treated with Hepatic Arterial Infusion Chemotherapy after Systemic Chemotherapy Was Difficult to Administer].

The patient underwent partial sigmoid colon resection for sigmoid colon cancer with hyper CEA blood(1,110.6 ng/mL) and concurrent liver metastases mostly in the right lobe of the liver, followed by systemic chemotherapy(SOX plus BEV). Seven courses of chemotherapy resulted in PR on imaging, and CEA was reduced to 5.0 ng/mL, which was within reference values. As he continued chemotherapy, frequent hematologic toxicities and adverse events forced frequent dose reductions and changes in the chemotherapy schedule. About 2 years after surgery(19 courses of SOX plus BEV), the liver metastases became slightly enlarged on imaging, and the CEA was also increasing. The patient did not wish to undergo systemic chemotherapy and requested hepatic arterial infusion chemotherapy(HAIC), which has relatively few side effects and adverse events. HAIC with pyrimidine fluoride alone is ongoing for 22 courses, and tumor markers have decreased again with PR on imaging. Performance status has been good without hematologic toxicity or adverse events for approximately 1 year during the course of HAIC. HAIC is a weakly recommended therapy in the colorectal cancer treatment guidelines, but it is considered one of the most effective therapies with relatively few side effects.

[A Case of Complete Remission in a Patient with Synchronous Double Cancers of the Breast and Lung].

The patient is a 74-year-old woman. She had breast cancer(invasive ductal carcinoma, ER[+], PgR[+], HER2[-], Ki-67: 30-40%)and primary right lung cancer with lumbar metastasis, which led to the diagnosis synchronous double cancers of the breast and the lung. We decided to precede surgery for lung cancer because breast cancer was indicated hormonal receptor positive. Breast cancer is treated with anastrozole, thoracoscopic right upper lobectomy was performed for the lung cancer. Radiation therapy was performed for metastatic bone tumors. 13 months later, partial mastectomy sentinel lymph node biopsy performed. The histopathological diagnosis of breast cancer was pT2, pN0, cM0, pStage ⅡA, and histological response was Grade 2a. The remaining breast was treated radiation therapy. The breast cancer has not recurred and is doing well 6 months after surgery. As for primary lung cancer, 19 months have passed since surgery, and the patient is in complete remission without recurrence.

[A Case of Small Intestinal Metastasis from Lung Cancer].

An 88-year-old man underwent thoracoscopic lower lobectomy for left lung cancer at the age of 87. Ten months later, he was examined closely for abdominal distention, frequent constipation, and anemia with a decreased Hb of 6.1 g/dL. The CT scan revealed an irregular tumor with contrast effect. The patient was diagnosed with malignant tumor of small intestine. At laparotomy, a tumor of 5 cm in diameter was found in the jejunum, and small bowel resection was done. Pathological examination revealed that the tumor was a metastasis of lung cancer. Seven months later, the patient is currently an outpatient, with no evidence of cancer recurrence.

Spatial and single-cell transcriptome analysis reveals changes in gene expression in response to drug perturbation in rat kidney.

The kidney is a complex organ that consists of various types of cells. It is occasionally difficult to resolve molecular alterations and possible perturbations that the kidney experiences due to drug-induced damage. In this study, we performed spatial and single-cell transcriptome analysis of rat kidneys and constructed a precise rat renal cell atlas with spatial information. Using the constructed catalogue, we were able to characterize cells of several minor populations, such as macula densa or juxtaglomerular cells. Further inspection of the spatial gene expression data allowed us to identify the upregulation of genes involved in the renin regulating pathway in losartan-treated populations. Losartan is an angiotensin II receptor antagonist drug, and the observed upregulation of the renin pathway-related genes could be due to feedback from the hypotensive action of the drug. Furthermore, we found spatial heterogeneity in the response to losartan among the glomeruli. These results collectively indicate that integrated single-cell and spatial gene expression analysis is a powerful approach to reveal the detailed associations between the different cell types spanning the complicated renal compartments.

[The Short-Term and Long-Term Outcomes of Laparoscopic and Open Distal Gastrectomy].

We compared laparoscopic gastrectomy and open gastrectomy for the early gastric cancer. Laparoscopic surgery was comparable to laparotomy in terms of operation time and number of lymph node dissections, significantly less bleeding volume, postoperative hospital stay, and lower postoperative complication rate. As a result of E-PASS, surgical invasion was significantly low and the overall risk score was also significantly low. There was no difference in cancer-specific survival, and overall survival was significantly better with laparoscopic distal gastrectomy. Based on the above, laparoscopic gastrectomy is considered to be superior to open gastrectomy as a surgical technique for the early gastric cancer.

[A Case of Rectal GIST under Long-Term Follow-Up with Oral Imatinib].

The patient was a 79-year-old man with complaints of defecation difficulties and constipation. CT scan showed a 7.5 cm diameter mass in the lower rectum, and biopsy revealed GIST. MRI findings suggested prostate invasion, and the patient was started treatment with imatinib. Six months later, the tumor shrank to 4.5 cm in diameter. However, the patient refused surgery and continued taking Imatinib. The tumor continued to shrink gradually. Currently, 7 years later at the age of 86, it is only 2 cm in diameter and its inside has almost completely been replaced with calcifications.

[A Case of Colon Cancer with Synchronous Multiple Metastases Successfully Treated with Combined Chemotherapy].

A 68-year-old man having a descending colon cancer with multiple metastases of up to 9.5 cm in the right lobe of the liver(T3, N0, M1a)underwent laparoscopic colon resection for anemia control. Chemotherapy with mFOLFOX6 plus Bmab was administered postoperatively. Because this treatment had little effect, FOLFIRI plus Pmab was initiated 3 months later. A significant reduction in the tumor size was observed. Therefore, we performed laparotomy. However, the liver metastasis had invaded the inferior vena cava, which was not resectable. After the second surgery, we introduced the 5-FU hepatic arterial injection port ia plus Pmab iv, which was effective for 8 months. We then restarted chemotherapy with FOLFIRI plus Pmab. However, the tumor became more enlarged; therefore, we changed the chemotherapy regimen to SOX plus Bmab. Partial reduction in the tumor size was observed again, and the effects lasted for a while. The patient continued visiting the outpatient clinic with almost no symptoms for more than 1 year. He died of the primary cancer 3 years and 8 months after the first visit. We report a case of liver metastasis of colon cancer that could have been controlled successfully by repeatedly using the same pharmacotherapy.

[A Case of Hyaline Vascular-Type Castleman's Disease].

The patient was a 29-year-old female with a chief complaint of transient right-sided abdominal pain. A CT scan revealed homogenously contrasted tumor of 4 cm in diameter with smooth margins and clear borders in the lower part of the pancreatic head. The tumor was contrast-enhanced on MRI and stained on abdominal angiography using the proximal branch of the right colonic artery as a feeding vessel. PET scan showed moderate accumulation. Malignancy could not be ruled out, and tumor resection including the ascending colon was performed. The pathological diagnosis was hyaline vascular-type Castleman's disease in the mesentery of the colon.

[Study on Gastric Cancer Surgery in an Aged Society].

We examined the occurrence of complications following gastric cancer surgery in the elderly and its influence on the prognosis of reduction surgery.The study included 805 surgical cases of gastric cancer; elderly, middle-aged, and young patients were examined.In the elderly patients, there was a tendency to undergo reduction surgery.According to the gastric cancer treatment guidelines, 28.9% of the elderly patients, 5.3% of the middle-aged patients, and 0% of the young patients did not satisfy the criteria for lymph node dissection. The incidences of postoperative complications were 25.6%, 23.0%, and 13.4%in the elderly, middle-aged, and young patients, respectively, with a higher tendency seen in elderly patients.In elderly patients, the survival rate was examined separately for each postoperative complication, but no significant difference was noted.Additionally, the survival rate was assessed for the limited surgery and standard surgery groups; however, no significant difference was noted.Therefore, it is recommended that the optimal lymph node dissection range be determined in the elderly with respect to the general condition.

[Comparison of Laparoscopic Gastrectomy and Open Gastrectomy Outcomes in the Elderly].

In this study, we compared the outcomes of laparoscopic gastrectomy and open gastrectomy in the elderly. Laparoscopic surgery was comparable to laparotomy in terms of the operation time and number of lymph node dissections and was significantly associated with less bleeding volume, duration of postoperative hospital stay, and a lower postoperative complication rate. Surgical invasion and overall risk scores were significantly low as assessed by the Estimation of Physiologic Ability and Surgical Stress(E-PASS)system. Based on these findings, laparoscopic gastrectomy can be considered to be superior to open gastrectomy as a surgical technique for the elderly.

[A Case of Unresectable Sigmoid Colon Cancer with Peritoneal Dissemination Treated with Chemotherapy after an Unintended Emergency Jejunostomy Formation].

A 33-year-old man was diagnosed with bowel obstruction due to advanced sigmoid colon cancer and underwent an emergency laparotomy. The sigmoid colon cancer turned out to be unresectable because of firm invasion to the retroperitoneum with severe adhesions and diffuse dissemination. Therefore, unplanned jejunostomy was performed, which was complicated by high-output stoma and short bowel syndrome. His condition was stable enough to receive chemotherapy via parenteral nutrition and parenteral electrolyte solution infusion added to the diet. mFOLFOX6 plus cetuximab therapy was started 4 weeks postoperatively. Although oxaliplatin was discontinued because of worsening numbness, he was sustained without cancer progression by receiving chemotherapy for a year. Chemotherapy was interrupted by a Candida fungemia 13months postoperatively, and he died 4 months later. Patients with jejunostomy may have difficulty absorbing enough water and nutrients in the intestine; therefore, they are at risk of dehydration and electrolyte depletions due to high stomal output, and malnutrition due to the short bowel. These complications may prevent colorectal cancer patients with jejunostomy to be indicated for chemotherapy.

[Stage â £ Breast Cancer with Difficulty in Initiating Chemotherapy-A Case Report].

We report a case of breast cancer(T4b[skin], N1, M1[lung], ER-, PR-, HER2 3+)in a 63-year-old woman with liver dysfunction of unknown cause(T-Bil 3.6mg/dL, ALP 3,483 U/L, AST 214 U/L, ALT 320 U/L, g / -GTP 1,943 U/L). Further- more, serum CA19-9(4,670 U/mL)and HbA1c(8.8%)levels were both elevated. First, she underwent chemotherapy with trastuzumab and capecitabine. Subsequently, liver dysfunction relieved gradually. CA19-9 and HbA1c levels were also decreased, but the tumor size was NC. Subsequently, trastuzumab, pertuzumab, and docetaxel were administered, as liver function became normal. The tumor shrank significantly after this treatment. Finally, she underwent mastectomy. Five years after the first visit, she has continued chemotherapy, with lung metastases almost scarred(CR).

[A Case of Successful Treatment with Gemcitabine plus Nab-Paclitaxel Therapy for Nonresected Pancreatic Body Cancer(Stage IVb)].

A 61-year-old woman was introduced for consultation with a chief complaint of frequent vomiting. CT revealed a pancreatic body cancer approximately 40mm in size; an invading stenosis from the horizontal part of the duodenum to the jejunum, superior mesenteric artery, and portal vein, splenic vein obstruction, lymphadenopathy, and some ascitic fluid. We diagnosed a passage disorder due to the invasive stenosis from the horizontal part of the duodenum of the pancreatic body cancer to the jejunum, and subsequently performed a duodenum and jejunum bypass operation. We controlled cancer pain with opioid analgesia, and S-1 monotherapy was chosen as the primary chemotherapy. A tendency to increase and the cancer pain of the tumor was aggravated when 5 courses took effect, so gemcitabine plus nab-paclitaxel(GEM plus nab-PTX)therapy was chosen as the second-line chemotherapy because of adverse Grade 3 events due to difficulties with S-1 internal use. We tapered off the opioid analgesia dosage because the cancer pain was relieved after 1 course. The imaging top indicated stable disease at the end of 5 courses, but the pain was relieved so opioid pain killers were unnecessary. Foreign continuation is under treatment with 10-course GEM plus nab-PTX therapy after initial diagnosis. Currently, the patient has undergone 5 courses of S-1 for approximately 18 months, and has achieved stable disease. The only adverse events were nausea, fatigue, Grade 1 malaise, and Grade 2 alopecia, as detected with imaging.

[A Case of Advanced Rectal Cancer in Which Long-Term Disease-Free Survival Was Achieved by Multidisciplinary Therapy].

The is a case involving a 55-year-old man with advanced rectal cancer(type 3). MRI showed urinary tract and regional lymph node metastases without distant metastasis. The tumor was reduced(PR)after neoadjuvant chemotherapy(mFOL FOX6 plus Bmab, 4 courses). The patient underwent an abdominoperineal resection. Because infiltration of the tumor into the lower urinary tract was deep, it was also resected and repaired. The clip was placed to mark the repaired region. Pathological examination revealed that excision stump at the anterior wall of the urethra was cancer positive without lymph node metastasis. He was then administered chemotherapy(mFOLFOX6 4 courses)and irradiated 60 Gy in both sides of the inguinal lymph node to prevent metastasis to the pelvicdomain. One year and 6 months postoperatively, as the left inguinal lymph node swelled at 3.7 cm irregularly, he further received chemotherapy(FOLFIRI 8 courses). The size of the lymph node became normal with a good response to FOLFIRI. Six years postoperatively, he remains alive and well with no evidence of recurrence.

Distributional shift of urea production site from the extraembryonic yolk sac membrane to the embryonic liver during the development of cloudy catshark (Scyliorhinus torazame).

Urea is an essential osmolyte for marine cartilaginous fishes. Adult elasmobranchs and holocephalans are known to actively produce urea in the liver, muscle and other extrahepatic organs; however, osmoregulatory mechanisms in the developing cartilaginous fish embryo with an undeveloped urea-producing organ are poorly understood. We recently described the contribution of extraembryonic yolk sac membranes (YSM) to embryonic urea synthesis during the early developmental period of the oviparous holocephalan elephant fish (Callorhinchus milii). In the present study, to test whether urea production in the YSM is a general phenomenon among oviparous Chondrichthyes, we investigated gene expression and activities of ornithine urea cycle (OUC) enzymes together with urea concentrations in embryos of the elasmobranch cloudy catshark (Scyliorhinus torazame). The intracapsular fluid, in which the catshark embryo develops, had a similar osmolality to seawater, and embryos maintained a high concentration of urea at levels similar to that of adult plasma throughout development. Relative mRNA expressions and activities of catshark OUC enzymes were significantly higher in YSM than in embryos until stage 32. Concomitant with the development of the embryonic liver, the expression levels and activities of OUC enzymes were markedly increased in the embryo from stage 33, while those of the YSM decreased from stage 32. The present study provides further evidence that the YSM contributes to embryonic urea homeostasis until the liver and other extrahepatic organs become fully functional, and that urea-producing tissue shifts from the YSM to the embryonic liver in the late developmental period of oviparous marine cartilaginous fishes.

Sulfate transporters involved in sulfate secretion in the kidney are localized in the renal proximal tubule II of the elephant fish (Callorhinchus milii).

Most vertebrates, including cartilaginous fishes, maintain their plasma SO4 (2-) concentration ([SO4 (2-)]) within a narrow range of 0.2-1 mM. As seawater has a [SO4 (2-)] about 40 times higher than that of the plasma, SO4 (2-) excretion is the major role of kidneys in marine teleost fishes. It has been suggested that cartilaginous fishes also excrete excess SO4 (2-) via the kidney. However, little is known about the underlying mechanisms for SO4 (2-) transport in cartilaginous fish, largely due to the extraordinarily elaborate four-loop configuration of the nephron, which consists of at least 10 morphologically distinguishable segments. In the present study, we determined cDNA sequences from the kidney of holocephalan elephant fish (Callorhinchus milii) that encoded solute carrier family 26 member 1 (Slc26a1) and member 6 (Slc26a6), which are SO4 (2-) transporters that are expressed in mammalian and teleost kidneys. Elephant fish Slc26a1 (cmSlc26a1) and cmSlc26a6 mRNAs were coexpressed in the proximal II (PII) segment of the nephron, which comprises the second loop in the sinus zone. Functional analyses using Xenopus oocytes and the results of immunohistochemistry revealed that cmSlc26a1 is a basolaterally located electroneutral SO4 (2-) transporter, while cmSlc26a6 is an apically located, electrogenic Cl(-)/SO4 (2-) exchanger. In addition, we found that both cmSlc26a1 and cmSlc26a6 were abundantly expressed in the kidney of embryos; SO4 (2-) was concentrated in a bladder-like structure of elephant fish embryos. Our results demonstrated that the PII segment of the nephron contributes to the secretion of excess SO4 (2-) by the kidney of elephant fish. Possible mechanisms for SO4 (2-) secretion in the PII segment are discussed.

[Two Cases of Lung Metastasis from Breast Cancer Successfully Treated with Endocrine Therapy].

We report 2 cases of lung metastasis from breast cancer that were successfully treated with endocrine therapy.Case 1 is a 69-year-old woman with cirrhosis of the liver caused by hepatitis C.She underwent surgery for left breast cancer at the age of 58, and surgery for right breast cancer at the age of 65.Four years later, she was diagnosed with lung metastasis of breast cancer.She received letrozole and the treatment was effective.Because the severity of the pleural effusion increased 3 years later, fulvestrant was subsequently administered.As a result, the patient remained in good health for 1 year.She died 5 years later.Case 2 is a 72-year-old woman who underwent right breast cancer surgery 12 years previously.She complained of respiratory discomfort as a result of right pleural effusion from lung metastasis.She was hospitalized for cancer lymphangitis that had deteriorated.The patient was immediately treated with fulvestrant and her symptoms improved significantly; the pleural effusion also disappeared.Sixteen months later, no recurrence has been observed.

Morphological and molecular investigations of the holocephalan elephant fish nephron: the existence of a countercurrent-like configuration and two separate diluting segments in the distal tubule.

In marine cartilaginous fish, reabsorption of filtered urea by the kidney is essential for retaining a large amount of urea in their body. However, the mechanism for urea reabsorption is poorly understood due to the complexity of the kidney. To address this problem, we focused on elephant fish (Callorhinchus milii) for which a genome database is available, and conducted molecular mapping of membrane transporters along the different segments of the nephron. Basically, the nephron architecture of elephant fish was similar to that described for elasmobranch nephrons, but some unique features were observed. The late distal tubule (LDT), which corresponded to the fourth loop of the nephron, ran straight near the renal corpuscle, while it was convoluted around the tip of the loop. The ascending and descending limbs of the straight portion were closely apposed to each other and were arranged in a countercurrent fashion. The convoluted portion of LDT was tightly packed and enveloped by the larger convolution of the second loop that originated from the same renal corpuscle. In situ hybridization analysis demonstrated that co-localization of Na(+),K(+),2Cl(-) cotransporter 2 and Na(+)/K(+)-ATPase α1 subunit was observed in the early distal tubule and the posterior part of LDT, indicating the existence of two separate diluting segments. The diluting segments most likely facilitate NaCl absorption and thereby water reabsorption to elevate urea concentration in the filtrate, and subsequently contribute to efficient urea reabsorption in the final segment of the nephron, the collecting tubule, where urea transporter-1 was intensely localized.

[A Case of Gastric Cancer with Adrenal Metastasis That Responded to Chemotherapy].

A 69-year-old man complained of abdominal pain and appetite loss. Advanced gastric cancer with bilateral adrenal metastases( stage Ⅳ)was revealed via an examination. XP(cisplatin and capecitabine)chemotherapy was administered. As a result, the tumor was reduced prominently, and his symptoms disappeared 3 months later. However, the cancer recurred 7 months later. Because of the tumor growth, the stent was detained for a passage obstacle by local increase of the tumor 12 months later. The patient died 14 months later.

Morphological and functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption.

For adaptation to high-salinity marine environments, cartilaginous fishes (sharks, skates, rays, and chimaeras) adopt a unique urea-based osmoregulation strategy. Their kidneys reabsorb nearly all filtered urea from the primary urine, and this is an essential component of urea retention in their body fluid. Anatomical investigations have revealed the extraordinarily elaborate nephron system in the kidney of cartilaginous fishes, e.g., the four-loop configuration of each nephron, the occurrence of distinct sinus and bundle zones, and the sac-like peritubular sheath in the bundle zone, in which the nephron segments are arranged in a countercurrent fashion. These anatomical and morphological characteristics have been considered to be important for urea reabsorption; however, a mechanism for urea reabsorption is still largely unknown. This review focuses on recent progress in the identification and mapping of various pumps, channels, and transporters on the nephron segments in the kidney of cartilaginous fishes. The molecules include urea transporters, Na(+)/K(+)-ATPase, Na(+)-K(+)-Cl(-) cotransporters, and aquaporins, which most probably all contribute to the urea reabsorption process. Although research is still in progress, a possible model for urea reabsorption in the kidney of cartilaginous fishes is discussed based on the anatomical features of nephron segments and vascular systems and on the results of molecular mapping. The molecular anatomical approach thus provides a powerful tool for understanding the physiological processes that take place in the highly elaborate kidney of cartilaginous fishes.