Granular C3 dermatosis-A report of two cases and a mini-review of literature.

Granular C3 dermatosis (GCD) is characterized by bullous, erythematous, and eczematous skin lesions similar to dermatitis herpetiformis, and granular deposition of complement C3 and C5b-9 along the epidermal basement membrane zone (BMZ) by direct immunofluorescence (IF). Here, we present two cases of GCD with different clinical features. Case 1, a 49-year-old man, showed pruritic blisters and erythema of the extremities. Case 2, a 53-year-old woman, showed severely pruritic papules, erythema, and erosions on the entire body with scattered blisters, mainly on the lower extremities. Both patients showed mild eosinophilia on blood tests, subepidermal blisters and prominent eosinophilic infiltration in the upper dermis on histopathological examination, and granular BMZ deposition of C3, but not of immunoglobulins or other complement components, on direct IF. No circulating autoantibodies were detected on enzyme-linked immunosorbent assays, chemiluminescent enzyme immunoassays, indirect IF using 1 mol/L NaCl-split normal human skin, or immunoblotting. Diagnosis of GCD was made in both cases. Case 1 was successfully treated with topical steroids, oral minocycline, and nicotinamide without any recurrence of symptoms. Case 2 was treated with oral steroids and showed remarkable improvement, although mild pruritic papules remained. We reviewed 30 reported GCD cases, including the two cases presented here, since Hashimoto et al. first described GCD in 2016. GCD should be more widely recognized, and further accumulation and validation of cases are required.

Bowen disease with sebaceous differentiation arising from clonal seborrheic keratosis.

We present a rare case of clonal seborrheic keratosis (SK) with focal Bowen disease (BD) (squamous cell carcinoma in situ) accompanied by sebaceous differentiation. An 89-year-old woman presented with a pale reddish-brown plaque on the left buttock. Histopathological examination of the excisional specimen revealed hyperkeratosis, acanthosis, and intraepidermal epithelioma. In some areas of the tumor, we observed proliferation of basaloid keratinocytes within the intraepidermal nests and pseudohorn cysts. This area was diagnosed as clonal SK. However, in other areas, the tumor cells within the intraepidermal nests showed nuclear pleomorphism, abnormal mitoses, dyskeratotic cells, and clumping cells, consistent with BD with a nested/clonal pattern (clonal BD). The SK and BD areas were contiguous with the transitional zone. Some nests within the BD area contained vacuolated cells with bubbly cytoplasm and scalloped nuclei, suggestive of sebaceous differentiation. Therefore, we made the diagnosis of clonal BD with sebaceous differentiation arising from clonal SK. All areas contained intraepidermal nests, which revealed that the lesions were not the result of accidental collision, but that the neoplastic cells in the intraepidermal nests of the SK transformed into BD and underwent sebaceous differentiation.

A case of Muir-Torre syndrome with a keratoacanthoma and sebaceous neoplasms: Clinicopathological features and a speculation on the pathogenesis of cutaneous tumor type.

Muir-Torre syndrome is a hereditary condition characterized by occurrence of sebaceous neoplasms or keratoacanthomas and visceral tumors. The most common mechanism for this syndrome is a constitutional defect in the mismatch repair genes. We report the case of a 67-year-old woman with a mutator L homologue 1 (MLH1) mutation. She had a history of endometrial and colorectal cancers. The patient presented with a typical keratoacanthoma on the right cheek and numerous sebaceous neoplasms on the face and trunk. Seven sebaceous adenomas and a low-grade sebaceous carcinoma were excised. Most sebaceous adenomas showed dermoscopic features such as some yellow comedo-like globules and curved vessels in creamy-white areas. Moreover, they revealed pathological features such as keratoacanthoma-like architecture and peritumoral or intratumoral lymphocytes. One of these sebaceous adenomas indicated histopathologically spontaneous regression and another was continuous with the hair follicle. Immunohistochemical staining for mismatch repair proteins revealed loss of expression for MLH1 and postmeiotic segregation increased 2 (PMS2) proteins in tumor cells nuclei in both keratoacanthoma and sebaceous adenoma. Nuclei in overhanging epithelial lips of the keratoacanthoma were also negative. These findings suggest that the type of Muir-Torre syndrome-related cutaneous tumor may have been affected by mismatch repair protein deficient sites in the pilosebaceous unit.

[Combined use of continuous epidural anesthesia nand transversus abdominis plane block for postoperative management of cesarean delivery in a patient whose previous cesarean deliveries were not properly controlled].

We report the successful combined use of continuous epidural anesthesia and transversus abdominis plane block for the management of postoperative pain following a cesarean delivery in a patient whose paralysis and pain were not well controlled after two previous cesarean deliveries. A 28-year-old female patient with no remarkable medical history was scheduled to undergo cesarean delivery at 38 weeks and 3 days of pregnancy. She had undergone cesarean deliveries twice previously, at 23 and 25 years of age. Both of these procedures were concluded using combined spinal-epidural anesthesia. However, in both procedures, the continuous epidural catheter could not be removed within 12 hours because of paralysis of the right leg and sharp pain. Therefore, during the third operation, the concentration of the continuous epidural anesthesia infusion was decreased to prevent complications, and a transversus abdominis plane block was added. The patient experienced no postoperative pain and fewer complications. We think that the combined use of these blocks provided good postoperative pain control with fewer complications.

[A clinical case of recurrent small intestinal cancer successfully treated with FOLFOX6].

A 73-year-old man was referred to our hospital because of ileus. Enteroscopy revealed severe stenosis in the jejunum. He was diagnosed with small intestinal cancer. Partial resection of the jejunum, partial resection of the transverse colon, and lymphadenectomy were performed. A postoperative pathological examination showed skip metastasis in the jejunum (TNM: Stage IV). Six months later, lung and liver metastases were evident from computed tomography( CT). Nine courses of FOLFOX6 administered once every 2 weeks achieved a partial response. When 9 courses of chemotherapy had been completed, CT showed progressive disease. Subsequently, he has been administered with FOLFIRI in our outpatient clinic.

[A case of liposarcoma of the abdominal wall complicated by thrombocytpenia as a paraneoplastic syndrome].

A 59-year-old woman was admitted to our hospital because of right chest pain. CT scan showed a mass on the right abdominal wall and bilateral pleural effusion. The histological diagnosis following core needle biopsy was undifferentiated sarcoma. The right pleural effusion gradually increased despite negative cytology. Although we planned chemotherapy for the clinically diagnosed pleural invasion, thrombocytopenia as a paraneoplastic syndrome appeared. The minimum thrombocyte count was 4,000/mm3. While transfusion was not effective, per os dexamethasone at 2.0 mg/day kept the thrombocyte count at around 6×10 4/mm3. Anti-thrombocyte antibody was negative. Tumor resection surgery with partial diaphragm resection and 11th and 12th rib resection, and abdominal wall plasty with mesh was performed. The final histological diagnosis was dedifferentiated liposarcoma. The thrombocyte count returned to the normal range just after the operation. However, she died of pleural dissemination, peritoneal dissemination, and local recurrence 69 days after the operation.

[A clinical case of the esophagogastric malignancy palliated with covered metallic stent with anti-reflux mechanism].

Esohophageal stents are often used in treating malignant stricture. But, when stents are placed across the esophagogastric junction, they may lead to esophagogastric reflux. We report a case of successfully treated esophagogastric strictures using the new stent with anti-reflux mechanism (long cover type Niti-S™ esophageal stent). A 78-year-old man presenting with severe strictures from the lower esophagus to cardiac part of stomach was histopathologically diagnosed as adenocarcinoma. CT scan images showed multiple liver metastatic tumors. However, he refused chemotherapy. Palliation using long cover type Niti-S™ esophageal stent was performed. No adverse effect was occurred. He started solid meals on the 7th postoperative day. He was thereafter able to ingest solid meals without the symptom of esophgogastric reflux and stenosis until he died of the primary disease two month later.

Parthenolide, an NF-κB inhibitor, suppresses tumor growth and enhances response to chemotherapy in gastric cancer.

AIM: This study evaluated the sesquiterpene lactone parthenolide, an inhibitor of transcription factor nuclear factor-kappaB (NF-κB), in the treatment of gastric cancer in vitro and in vivo. MATERIALS AND METHODS: In vitro, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to evaluate the effect of parthenolide on growth inhibition and chemosensitization to antitumor drugs of three gastric cancer cell lines (MKN-28, MKN-45 and MKN-74). Microarray analysis was performed to identify genes which were up- or down-regulated on the treatment of parthenolide. The isobologram analysis was introduced to evaluate the synergic effect of parthenolide on antitumor drugs. In vivo, the effect of parthenolide was investigated in a mouse peritoneal dissemination model with and without chemotherapy. RESULTS: Parthenolide significantly inhibited cell growth in three gastric cancer cell lines. The phosphorylation of NF-κB was down-regulated by the treatment of parthenolide. The synergic effect of parthenolide was confirmed in combination with paclitaxel and cisplatin. In the peritoneal dissemination model, parthenolide significantly suppressed the disseminated nodules as a single agent and also enhanced chemosensitivity to paclitaxel. Furthermore, the combined therapy of parthenolide and paclitaxel significantly contributed to prolonging the survival duration. CONCLUSION: The NF-κB inhibitor, parthenolide, may enhance chemosensitivity to paclitaxel in the treatment of patients with gastric cancer.

[A clinical case of lymph node recurrence after resection of gastric cancer successfully treated by combination chemotherapy with irinotecan and cisplatin].

A 60-year-old female who was diagnosed as gastric cancer underwent distal gastrectomy and received adjuvant chemotherapy (S-1 therapy). After 6 months, the tumor marker (CEA) was elevated. CT revealed para-aortic lymph nodes enlargement. Lymph node metastasis was confirmed. The patient was administered combination chemotherapy with irinotecan (CPT-11) and cisplatin (CDDP) Seven months later, CT revealed lymph node metastasis had disappeared. After judgment of complete response (CR), we continued the treatment for 22 months. The patient was followed without any recurrence in May 2010.

[Three cases of breast cancer with skin metastasis after mastectomy treated by radiotherapy].

We reported three cases of patient with triple negative skin metastasis after mastectomy of breast cancer. All three cases had received radiotherapy for skin metastasis. Radiation therapy was effective for recurrent sites, and could improve patient's QOL. After radiotherapy, 2 patients died due to a distant metastasis. Case 1 was resistant to chemotherapy. Case 2 was no indication of chemotherapy because of dementia metastases. Case 3 was the only one continued chemotherapy. It appears that a further consideration was needed for the timing of radiotherapy to be performed among the treatments of locoregional recurrence and distant metastasis of breast cancer.

[Two cases of bronchiolitis obliterans organizing pneumonia (BOOP) induced radiotherapy after surgery of breast cancer].

We report two cases of bronchiolitis obliterans organizing pneumonia (BOOP) induced radiotherapy after surgery of breast cancer. One of the patients was a 58-year-old woman. She underwent a conserving surgery for bilateral breast cancers, and received radiation therapy to the remaining part of bilateral breasts. Two months after the termination of irradiation, cough, fever and general fatigue developed. We clinically diagnosed this case as BOOP after radiation therapy. After initiation of oral steroid therapy, the clinical symptoms and radiographic findings disappeared. Another patient was a 57-year-old woman. She underwent radical mastectomy for right breast cancer. A month after the operation, she suffered from local recurrence, so radiation therapy to the thoracic wall was performed. After irradiation, resection of the thoracic wall lesion was performed because of malignancy from local skin biopsy specimen. Two months after the termination of irradiation, cough, dyspnea and fever developed. We clinically diagnosed this case as radiation-induced BOOP by BAL and TBLB findings. After an initiation of steroid therapy, the clinical symptoms and radiographic findings disappeared. It is important to be aware of BOOP as a complication in the patient who was given radiation after surgery of breast cancer.

[A case of surgical approach to the recurrence of the para-aortic lymph nodes after resection of rectal cancer].

A 63-year-old female diagnosed as rectal cancer underwent low anterior resection and received adjuvant chemotherapy (folinate/tegafur/uracil therapy). After 6 months, lymph node metastasis was confirmed by an elevation of the tumor marker (CEA) and a FDG-PET image. After administration of 37 courses of mFOLFOX6 therapy, surgical excision was performed to the lymph node recurrence, because it was difficult to continue mFOLFOX6 therapy with grade 3 neuropathy. After 8 months from the last operation, no lymph node metastasis was appeared in the para-aortic area.

Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy.

BACKGROUND: In neoadjuvant chemotherapy for advanced esophageal cancers, complete tumor regression has been difficult to achieve, and tumor often remained after chemotherapy. However, the best method for evaluating the response to chemotherapy based on histopathologic examination of residual tumors has not been established. METHODS: Studied were 74 patients who received neoadjuvant chemotherapy (5-fluorouracil, cisplatin, and doxorubicin), followed by surgery for advanced esophageal squamous cell carcinoma. The correlation between various histopathologic factors and clinical response with survival was examined, including the importance of tumor budding in the invasive front of tumors on clinical response and survival. RESULTS: Among 74 patients, 3 achieved a pathologic complete response, and 29 (41%) of 71 residual tumors demonstrated high-grade budding in the invasive front. The 5-year survival rate of patients with low-grade budding tumors was 49%, compared with 17% for those with high-grade budding (P < .001). Budding correlated inversely with good response, which was observed in 44 (60%) of 74 patients. Univariate analysis showed that pathologic tumor depth, number of lymph node metastases, pathologic stage, lymphatic invasion, budding and clinical response were significant prognostic factors. Multivariate analysis identified budding as the most important prognostic factor followed by number of lymph node metastases. CONCLUSIONS: The results of the current study indicated that tumor budding in the invasive front of tumors correlated significantly with clinical response and prognosis of patients with esophageal squamous cell carcinomas who received neoadjuvant chemotherapy. However, the mechanism of tumor budding in the invasion front of esophageal squamous cell carcinomas treated with chemotherapy was not clarified.

[The efficacy of surgical resection and chemo-endocrine therapy for patients with local recurrence or axillary lymph node metastasis of breast cancer].

We evaluated a surgical resection and chemo-endocrine therapy and prognosis for patients with local recurrence or axillary lymph node metastasis of breast cancer. Twenty-one patients with local recurrence or axillary lymph node metastasis without a distant metastasis were enrolled in this study. Thirteen of the 21 patients underwent a surgical resection. Resection of recurrent lesion in residual breast after breast conserving therapy for six of the 13 patients, axillary lymph node dissection (ALND) for four, and resection of thoracic wall lesion for three were performed. Five of the patients who underwent resection of residual breast lesion, four of the patients who underwent ALND and two of the patients who underwent resection of thoracic wall lesion have survived. One of the patients who underwent resection of residual breast lesion and one of the patients who underwent resection of thoracic wall lesion were dead. In eight non-operable patients, five were dead and three have survived. Median recurrence free interval was 24 months in operable patients and 27 months in non-operable patients. Median survival time after recurrence was 29 months in operable patients and 12 months in non-operable patients. The surgical with chemo-endocrine therapy promises to control well to local recurrence or axillary lymph node metastasis for the patients we selected.

LC3, an autophagosome marker, is highly expressed in gastrointestinal cancers.

Autophagy is a bulk protein and organelle degradation process essential for cell maintenance and viability. Microtubule-associated protein 1 light chain 3 (LC3), the mammalian homologue of yeast Atg8, is involved in autophagosome formation during autophagy. The aim of this study was to investigate LC3 expression in gastrointestinal cancers to elucidate the role of autophagy in human cancer development. We evaluated LC3 expression by immunohistochemistry in 163 gastrointestinal cancers including 106 esophageal, 38 gastric and 19 colorectal cancers. Seventy precancerous intraepithelial neoplasias were found in esophageal cancer specimens. LC3 expression was compared with Ki-67 staining and expression of carbonic anhydrase (CA) IX, a hypoxic marker. LC3 was expressed in the cytoplasm of cancer cells, but not in noncancerous epithelial cells. A high expression of LC3 was observed in 53% of esophageal, 58% of gastric and 63% of colorectal cancers. LC3 immunoreactive score gradually increased during early esophageal carcinogenesis in low- and high-grade intraepithelial neoplasia and T1 carcinoma, while it did not change in later cancer progression (T2-T4 carcinomas). In early esophageal carcinogenesis, LC3 expression correlated with Ki-67 labeling index (p=0.0001), but showed no significant association with CAIX expression. In esophageal cancers, LC3 expression did not correlate with various clinicopathological factors, including survival. LC3 is upregulated in various gastrointestinal cancers and partly associated with Ki-67 index. Our results suggest that LC3 expression is advantageous to cancer development especially in early-phase carcinogenesis.

The activation of Akt during preoperative chemotherapy for esophageal cancer correlates with poor prognosis.

The activation of the PI3K/Akt/mTOR pathway plays an important role in tumorigenesis and resistance to anticancer drugs. The aim of this study was to elucidate the role of the Akt/mTOR pathway in chemoresistance and the prognosis of patients with esophageal squamous cell carcinoma (ESCC) who received preoperative chemotherapy. We evaluated p-Akt and p-mTOR expression by immunohistochemistry in the surgical specimens of 143 ESCC (51 patients with and 92 without preoperative chemotherapy). In 37 patients of the former group, paired tissue samples obtained before and after chemotherapy were examined immunohistochemically. The incidence of p-Akt expression was higher in ESCC with than without chemotherapy (51.0 vs. 25.0%, p=0.0018). Although p-Akt expression was not associated with an advanced tumor stage, a comparison between before and after chemotherapy demonstrated an increased p-Akt expression during chemotherapy (p=0.0348). The p-Akt expression did not correlate with survival in ESCC without chemotherapy, but was associated with poor prognosis in those with chemotherapy (p=0.0058). In particular, an increased p-Akt expression during chemotherapy was associated with poor survival (p=0.0022). Notably, the p-mTOR expression did not correlate with p-Akt expression (p=0.1482). The depth of the tumor invasion, clinical response and p-Akt expression correlated with the prognosis of 51 ESCC with chemotherapy. A multivariate analysis showed that p-Akt expression was the only independent predictor of poor prognosis in ESCC patients with chemotherapy. p-Akt expression increases after chemotherapy in ESCC and a high expression correlates with poor prognosis. Our results suggest that the activation of Akt is a potentially useful therapeutic target in ESCC patients treated with chemotherapy.