[Effects of Conservative or Surgical Treatment of Anastomotic Leakage after Colorectal Surgery].

BACKGROUND: Anastomotic leakage is associated with short- and long-term mortality and an increased risk of local and distant cancer recurrence. This study aimed to investigate the short- and long-term outcomes after surgical or conservative therapy for anastomotic leakage. METHODS: Patients with anastomotic leakage after undergoing colorectal resection between January 2011 and December 2018 were identified and grouped according to the therapy for anastomotic leakage: surgical or conservative. We analyzed the intergroup differences in clinicopathological factors and outcomes. RESULTS: Of the 33 patients with anastomotic leakage, 21(64%)and 12(36%)patients received surgical therapy and conservative therapy, respectively. Patients in the conservative therapy group had a shorter length of hospital stay after the first operation. In patients with UICC Stage Ⅱ/Ⅲ, both overall and recurrence-free survival were significantly worse in those who were treated conservatively than in patients who were surgically treated(p<0.01). CONCLUSION: Conservative therapy for anastomotic leakage could shorten the length of hospital stay, but could negatively affect long-term outcomes.

[A Case of Laparoscopic Hartmann's Operation for Perforation of Rectal Cancer in Superior Elderly People].

We report a case where home discharge was possible after laparoscopic Hartmann's operation for superior elderly perforation of rectal cancer. The patient was 91-year-old, a woman. She was delivered to the emergency room complaining of weakness. We diagnosed rectal perforation and started emergency laparoscopic surgery. Rectal cancer perforation was observed during surgery and laparoscopic Hartmann's operation plus D2 lymph node dissection was performed. The operation time was 3 hours 21 minutes, the blood loss was 10 g. She resumed her meal intake from the postoperative day(POD)5 and became ready for discharge on POD 20 postoperatively. She moved to a comprehensive care ward and she was discharged to her house on POD 89. On POD 120, she visited the hospital complaining of anorexia and anal bleeding, and was diagnosed as local recurrence in the pelvis, multiple liver metastases, and cancerous peritonitis. She was admitted to palliative care unit on POD 132 and died on POD 141. It was suggested that laparoscopic surgery will be minimally invasive even at superior elderly patients and that they will be able to discharge from their homes.

[A Case of a Patient with Multiple Liver Metastases of Colorectal Cancer with Relapse-Free, Long-Term Survival and Responding Completely to Chemotherapy after Primary Lesion Resection].

A 64-year-old man who suffered from colorectal cancer with multiple liver metastases underwent laparoscopic low anterior resection. He did not undergo partial liver resection. He was treated with mFOLFOX6 plus bevacizumab chemotherapy. The liver metastases had disappeared completely on Gd-EOB-DTPA(EOB)MRI after 6 courses of therapy with mFOLFOX6 plus bevacizumab. This chemotherapy was discontinued after 13 courses. At present, 86 months have passed since the laparoscopic low anterior resection. He is relapse-free and a long-term survivor.

Utility of Laparoscopic Subtotal Cholecystectomy with or without Cystic Duct Ligation for Severe Cholecystitis.

We use open cholecystectomy (OC) to treat severe cholecystitis in cases in which we are worried that inflammation might cause anatomical changes in Calot's triangle. Furthermore, in cases of severe cholecystitis in which marked inflammation leads to fibrosis, we perform subtotal cholecystectomy (SC), i.e., incomplete gallbladder resection. Laparoscopic SC (LSC) without cystic duct dissection is considered to be effective at reducing the incidence of serious complications in patients with severe cholecystitis. The cases of 246 patients who underwent cholecystectomy for benign gallbladder disease between January 2011 and May 2015 were evaluated retrospectively. Of these patients, 14 were treated with LSC, and 19 underwent OC. Moreover, three patients in the LSC group underwent LSC without cystic duct ligation because it was considered that it would be difficult to dissect and ligate the cystic duct. The LSC group suffered significantly less intraoperative blood loss than the OC group. However, the operative times of the two groups were similar. Moreover, the duration of the postoperative hospitalization period was significantly shorter in the LSC group than in the OC group. Next, we compared the long-term outcomes of the SC and total cholecystectomy groups, regardless of the surgical method. No cases of cholecystitis or gallbladder cancer were encountered in either group. It is suggested that LSC is safe, effective, and helps to prevent serious complications in cases of severe cholecystitis that require conversion to OC, regardless of whether cystic duct ligation is performed.

[Long-Term Survival of a Patient with Stage IV Breast Cancer and An Intrathoracic Space-Occupying Metastatic Lesion].

A 50-year old woman noticed left axillary lymph node swelling and presented at our hospital. CNB showed adenocarcinoma( pap-tub, ER+, PgR+, HER2 3+). CT revealed a right lung metastatic nodule and swollen lymph nodes above the left collarbone and left axilla. However, no breast tumor was found at that time. We diagnosed occult breast cancer, TxN3bM1 (lung), Stage IV . FEC(100), paclitaxel, letrozole, anastrozole, exemestane plus trastuzumab, tegafur/uracil plus trastuzumab, and lapatinib plus capecitabine were sequentially administered. Five years and 9 months after the treatment started, CT revealed a right intrathoracic lesion that had gradually increased in size. Subsequently, trastuzumab plus pertuzumab plus docetaxel, bevacizumab plus paclitaxel, trastuzumab emtansine, trastuzumab plus fulvestrant, and doxifluridine plus medroxyprogesterone acetate plus cyclophosphamide(DMpC therapy)were sequentially administered. At this time, 8 years after the treatment started, trastuzumab plus pertuzumab plus vinorelbine were also administered. An intrathoracic space-occupying lesion due to breast cancer is rare, and anti-HER2 chemotherapy was effective for this patient.

Penile pseudomyogenic hemangioendothelioma/epithelioid sarcoma-like hemangioendothelioma with a novel pattern of SERPINE1-FOSB fusion detected by RT-PCR--report of a case.

We experienced a rare case of penile mesenchymal tumor in a 43-year-old Japanese man. At least three nodules were observed around the penis. The tumors were composed of spindle- to oval-shaped atypical cells with and without prominent nucleoli. These cells were like myogenic cells, but negative for myogenic markers. They were positive for endothelial markers, such as ERG, Fli1 and CD31. They were also positive for nuclear and cytoplasmic FOSB which are not expressed in epithelioid hemangioendothelioma or epithelioid sarcoma. These pathological and immunohistochemical findings strongly suggested pseudomyogenic hemangioendothelioma/epithelioid sarcoma-like hemangioendothelioma (PHE/ES-HE). Since a recent report directly proved that two cases of PHE/ES-HE have SERPINE1-FOSB fusion gene by reverse transcription-polymerase chain reaction (RT-PCR), we examined whether the fusion gene is present or not in the present case by RT-PCR using fresh frozen surgical material. Sequencing of the PCR product revealed that this case has SERPINE1-FOSB fusion. The fusion pattern of our case was different from those of two previously reported cases. In our case, 86 nucleotides of SERPINE1 intron 1 were inserted between SERPINE1 exon 1 and the middle portion of FOSB exon 1, and a putative translation start codon was identified in SERPINE1 intron 1. Thus, this is the third case of PHE/ES-HE with SERPINE1-FOSB fusion proved by RT-PCR.

[A case of breast cancer with large cancer ulcer and multiple bone and liver metastasis responding to combination therapy of radiation and chemotherapy].

We report a case of breast cancer in a 58-year-old female patient. In 2005, she was hospitalized for therapy of left breast cancer. The tumor observed was accompanied by invasion of the skin and ribs. At the same time, multiple liver and bone metastases were also observed(solid tubular adenocarcinoma, ER(+), PgR(±), HER2(3+), T4NxM1, stage IV). She was started on radiation therapy and chemotherapy(paclitaxel+trastuzumab). While the liver and bone metastases remained unchanged, the primary focus became noticeably smaller. In the course of follow-up visits, we began to administer her paclitaxel biweekly. This treatment, however, worsened her liver metastases and led us to switch to combination chemotherapy with vinorelbine and capecitabine. After 6 courses of the therapy, her liver metastases disappeared and her tumor marker levels became normal. The combination chemotherapy was continued for 1 year and then followed by 18 months of chemotherapy with capecitabine alone until recurrence of liver metastases was observed. Capecitabine along with cyclophosphamide was orally administered, bringing her tumor marker levels down to the normal range again. After approximately 6 years from the start of treatment, the patient is still alive.

Interleukin-17- and protease-activated receptor 2-mediated production of CXCL1 and CXCL8 modulated by cyclosporine A, vitamin D3 and glucocorticoids in human keratinocytes.

Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor which mediates a variety of functions in the skin including cutaneous inflammation. SLIGKV-NH(2) , an agonist peptide for PAR2, enhanced the interleukin (IL)-17-induced production of two CXC chemokines, CXCL1 (GRO-α) and CXCL8 (IL-8), in normal human epidermal keratinocytes (NHEK) in a concentration-dependent manner. The enhanced production of those chemokines was suppressed by a PAR2-specific siRNA. The SLIGKV-NH(2) -induced production of both CXCL1 and CXCL8 was markedly reduced by cyclosporine A. The enhanced production of CXCL1 was suppressed by 1α, 24R-dihydroxyvitamin D(3) , an active form of vitamin D(3) , and weakly by glucocorticoids, dexamethasone and clobetasol propionate, whereas production of CXCL8 was not altered by any of those receptor agonists. In psoriatic skin, the thickened upper spinous layer of the epidermis was positive for PAR2 protein and the expression of the IL17A mRNA was increased. These results suggest that the IL-17-induced pro-inflammatory reaction is enhanced by the activation of PAR2 in keratinocytes, and that the effect of PAR2 is differentially modulated by cyclosporine A, the active form of vitamin D(3) and glucocorticoids.

Pneumatosis intestinalis leading to perioperative hypovolemic shock: Case report.

Pneumatosis intestinalis (PI) is an uncommon disorder defined as multiple foci of gas within the intestinal wall. Despite recognition of an increasing number of cases of PI, the optimal management strategy, whether through surgical or other means, remains controversial. The present report describes the case of a patient with PI who underwent exploratory laparotomy without specific findings and who ultimately died due to extensive intestinal hemorrhage that was possibly triggered by surgery.

Gastrointestinal Stromal Tumor in a Patient with Neurofibromatosis: Abscess Formation in the Tumor Leading to Bacteremia and Seizure.

A 66-year-old woman with neurofibromatosis type 1 (NF1) was brought to the emergency room with seizures and high-grade fever. Seizure in adult NF1 patients raises concern for intracranial lesions. However, neurological examination and central nervous system imaging failed to detect any causative intracranial lesions for her seizure. Gram-positive cocci, Streptococcus anginosus, were detected by blood cultures. Abdominal computed tomography revealed a well-defined round mass 7 cm in diameter, which was found to be a small intestinal gastrointestinal stromal tumor (GIST) containing an abscess. There was fistula formation between the intestinal lumen and the abscess, in which there were numerous Gram-positive cocci. The seizure may have been caused by hypoosmolality (hyponatremia and hypoproteinemia), which may result from decreased food intake associated with high-grade fever and general malaise. In this case GIST originating from the small intestine was invaded by S. anginosus through a fistula, leading to abscess formation, bacteremia, high-grade fever, and seizure, which was the first clinical manifestation.

[A case of S-1-resistant gastric cancer with multiple bone metastases and disseminated intravascular coagulation--effective treatment by combined chemotherapy with CDDP and CPT-11].

A 49-year-old female with advanced gastric cancer complicated with peritoneal dissemination underwent distal gastrectomy, and thereafter she was treated with a combined chemotherapy of S-1 and paclitaxel for 5 months, followed by treatment with S-1 alone. A year after the gastrectomy, she developed disseminated intravascular coagulation (DIC) with multiple bone metastases despite the continuous treatment with S-1, indicating that S-1 was no longer effective. She was then effectively treated by a combined chemotherapy with cisplatin(CDDP)and irinotecan hydrochloride (CPT-11), and DIC subsided within 7 days after the treatment. These findings suggest that combined chemotherapy with CDDP and CPT-11 is a useful regimen for the treatment of certain patients with DIC associated with S-1-resistant advanced gastric cancer.

Tetracyclines modulate protease-activated receptor 2-mediated proinflammatory reactions in epidermal keratinocytes.

In addition to their antibiotic effects, tetracyclines have anti-inflammatory action that is often beneficial in the control of inflammatory skin disorders. In this study, we examined the effects of tetracycline (TET) and two of its derivatives, doxycycline (DOX) and minocycline (MIN), on the production of interleukin-8 (IL-8) elicited by the activation of protease-activated receptor 2 (PAR2) in normal human epidermal keratinocytes (NHEK). In NHEK, the production of IL-8 stimulated by an agonist peptide of PAR2, SLIGKIV-NH(2), at 100 microM was significantly reduced by TET, DOX, or MIN at 5 and 10 microM, concentrations that are noncytotoxic. The tumor necrosis factor alpha (TNF-alpha)-induced production of IL-8 was synergistically augmented by SLIGKIV-NH(2), and that synergistic increase in the production of IL-8 was suppressed by 100 nM PAR2-specific small interfering RNA. It was also suppressed by TET, DOX, or MIN but not by the 14-membered-ring macrolide antibiotics erythromycin, roxithromycin, and clarithromycin, which also have anti-inflammatory activities, at 10 microM. These results suggest that tetracyclines attenuate the PAR2-IL-8 axis in keratinocytes and thereby effectively modulate proinflammatory responses in the skin.

Adult cutaneous alveolar rhabdomyosarcoma on the face diagnosed by the expression of PAX3-FKHR gene fusion transcripts.

A 26-year-old woman presented with an indurated subcutaneous tumor on her left cheek. The histology was compatible with alveolar rhabdomyosarcoma, but immunohistochemistry showed that the tumor cells were negative for desmin, alpha-smooth muscle actin and alpha-Sr-1, but were positive for CD56, vimentin and myogenin. The diagnosis of alveolar rhabdomyosarcoma was confirmed by the detection of PAX3-FKHR fusion gene transcripts in the paraffin-embedded tumor tissue. The tumor was unresponsive to chemotherapy with pirarubicin, carboplatin and ifosfamide, and the patient died 9 months after the diagnosis. This adult case of an alveolar rhabdomyosarcoma primarily occurring on the face is very rare, and the detection of PAX3-FKHR fusion gene transcripts was useful for diagnosis of the disease.