PHLDA1 expression in ulcerative colitis: A potential role in the management of dysplasia.

Pleckstrin homology-like domain, family A, member 1 (PHLDA1) is a protein involved in cell proliferation, adhesion and migration in colon cancer. In normal large intestinal mucosa, this protein is expressed only in the crypts. By contrast, its expression in adenomas and cancers of the large intestine is spread throughout the glandular ducts, and it has been reported that PHLDA1 may be involved in the process of carcinogenesis. PHLDA1 may also be involved in the pathogenesis of ulcerative colitis (UC). The expression levels of PHLDA1 in tissues from patients with UC were analyzed using immunohistochemistry, and its relationship with the development of UC-associated colorectal cancer (UC-CRC) was examined. Overall, tissue samples from 143 lesions (90 colitis lesions, 39 dysplastic lesions and 14 UC-CRC lesions) were prepared from excised specimens of 49 patients with UC who underwent surgery in Tokyo Medical and Dental University Hospital between January 2004 and December 2017. Subsequently, immunostaining for PHLDA1 was performed. PHLDA1 expression was evaluated in UC-CRC and dysplastic tissues within the entire lesion area on the slide and in colitis over the area of the accompanying duct. The cytoplasmic staining intensity was classified into four levels, and the expression score (0-2 points) was calculated. The median PHLDA1 expression score was 0.295 for colitis, 0.607 for dysplasia and 0.865 for UC-CRC. The dysplasia expression score was significantly higher than the colitis score (P<0.001), while the UC-CRC expression score was significantly higher than the dysplasia score (P=0.003). The expression levels of PHLDA1 in UC cases were higher in colitis, followed by dysplasia and UC-CRC, which suggested that this protein may be involved in the carcinogenesis of UC-CRC. In addition, PHLDA1 immunostaining may help in the diagnosis of dysplasia, which is a type of precancerous lesion.

[Evaluation of Skeletal Muscle Mass and Functions during Perioperative Period of Breast Cancer Patients].

Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass, strength and function. Sarcopenia has repeatedly been reported as a strong predictor of both short- and long-term outcomes following surgical treatment for breast cancer. In this study, 41 primary breast cancer cases who received surgery at our hospital were examined. To evaluate which factor amongst muscle volume, power or function would be most important to avoid sarcopenia after surgery, we examined muscle volume, power and function respectively. We also divided patients into groups by their ages or procedures of surgeries, then compared and analyzed within those groups. The results showed their grip power of the same side of their breast cancer and muscle volume of their legs has been decreased after surgeries. We also found patients who were equal or older than 75 years old and patients who received total mastectomy tended to lose their muscle volume or muscle power after their surgeries. These groups of patients would have potential risk to become sarcopenia after surgeries. It would be important to observe each of 3 factors, skeletal muscle volume, power and function to evaluate precisely their condition of sarcopenia. Tailor-made peri-operative rehabilitation programs, especially for elderly patients or patients who received total mastectomy, would be a possible solution to avoid sarcopenia after surgery for breast cancer.

[Meningeal Carcinomatosis of Sigmoid Colon Cancer-A Case Report].

A 60-year-old man with sigmoid colon cancer invading the urinary bladder underwent sigmoid colectomy and partial cystectomy. He developed headache and vomiting 12 weeks after surgery, and urgently hospitalized. Contrast MRI of head and whole spinal cord inspected no abnormality. CSF examination showed elevated CA19-9 20,551 U/mL, and the cytology revealed atypical cells similar to the sigmoid colon cancer cells. He was diagnosed as meningeal carcinomatosis, and received 1 course of CAPOX plus bevacizumab chemotherapy. He died 18 weeks after the surgery.

[A Case of Gastric Large-Cell Neuroendocrine Carcinoma Combined with Adenocarcinoma in the Cecum].

A 74-year-old man with anemia visited our department. Esophagogastroduodenoscopy showed a type 2 lesion from the angulus to the antrum. Histopathological findings indicated gastric neuroendocrine carcinoma. Colonoscopy showed a type 1 lesion at the cecum. Distal gastrectomy was performed with D1+lymph node dissection, Roux-en-Y reconstruction, and ileocecal resection with D3 lymph node dissection. The patient was pathologically diagnosed with large-cell neuroendocrine carcinoma in the stomach, pT4a(SE), med, INF a>>b-c, ly1-2, v1(SM, EVG), pN0, pM0, pStageⅡB, and adenocarcinoma (tub1>tub2)of the cecum, pT2(MP), ly1(HE), v1(EVG, SM), pN0, pM0, pStageⅠ. Postoperatively, he received oral S-1 as an adjuvant chemotherapy. His postoperative course was uneventful without any recurrence over 18 months.

[Two Cases of Rectal Cancer with Pelvic Local Recurrence Complicated with Sepsis after Rectal Cancer Surgery Successfully Treated with Radiation Therapy].

Treatment of rectal cancer with postoperative pelvic recurrence may complicate infection and may be difficult to treat. We experienced 2 cases complicated with sepsis due to infection in the pelvic local recurrence in which radiation therapy was performed and they were shifted to outpatient molecular-targeted drug therapy. Case 1 involved a 58-year-old woman. In December 2011, colostomy and chemotherapy were performed for locally advanced rectal cancer. In June 2012, we performed low anterior resection. In January 2014, chemotherapy was started for pelvic recurrence. She discontinued treatment for 4 months due to personal circumstances. Recurrence was worsened, and infection caused sepsis and she was admitted to the hospital in February 2017. Infection was not improved with antibiotic drugs, and radiation therapy(60 Gy/30 times)was performed. Infection was improved, and panitumumab monotherapy was started and she was discharged. Case 2 involved a 61-year-old man. In February 2014, a lower anterior resection for rectal cancer was performed. In September 2015, chemotherapy was started for pelvic recurrence. In November 2016, chemotherapy was discontinued due to esophageal variceal rupture. Recurrence was worsened, and infection caused sepsis and he was admitted to the hospital in May 2017. Radiation therapy(50 Gy/20 times)was performed after colostomy. Infection was improved, and cetuximab monotherapy was started and he was discharged.

[Long-Term Survival of a Case with Brain and Lung Metastases from Resected Rectal Cancer by Gamma Knife Radiosurgery].

A 69-year-oldfemale hadund ergone low anterior resection for rectal cancer(Rb). Histological examination showedwell differentiated adenocarcinoma with lymph node metastasis. Adjuvant chemotherapy with UFT was performed postoperatively. Nineteen months later, abdominoperineal resection was performedfor anastomotic recurrence andS -1 chemotherapy was made. As 2 left lung metastases appearedat the 44 months after first surgery, capecitabine was performedfor 4 years. At the 101 months after first surgery, sensory difficulty of right lower limb appearedandMRI revealedbrain tumor(single, 18mm) in the left parietal lobe. We performedgamma knife radiosurgery for the brain metastasis andmultiagent chemotherapy for lung metastases. Although the brain metastases have relapsedtwice, gamma knife providedgoodlocal control. She is surviving without symptom of brain metastases 37 months after the detection.

[Two Cases of Colon Cancer with Severe Liver Dysfunction Due to Multiple Liver Metastases Effectively Treated with Hepatic Arterial Infusion Chemotherapy plus CetuximabFollowed by Systemic Chemotherapy].

Case 1: An 80-year-old man was diagnosed with cecal cancer plus multiple liver metastases and peritoneal disseminations. He underwent surgical resection of the primary tumor to prevent bowel obstruction. Initially, hepatic arterial infusion(HAI) plus cetuximab(Cmab)was administered to reduce the size of the metastatic tumors and prevent liver failure. A partial response(PR)was observed in the liver metastases after 12 courses of treatment and S-1 plus oxaliplatin(SOX)plus bevacizumab was started. Case 2: A 44-year-old man was diagnosed with sigmoid colon cancer with multiple liver, lung and bone metastases, and with obstructive jaundice and cholangitis due to severe liver hilum lymph node metastases. His performance status(PS)score was 3 because of severe liver damage. Initially, he underwent endoscopic nasobiliary drainage for obstructive jaundice, and HAI plus Cmab was started to prevent liver dysfunction and to control all metastases. A PR in the metastatic liver tumors was observed after 18 courses. His PS increased to 1 and he was treated with mFOLFOX6 plus Cmab. HAI plus Cmab might be a treatment option for patients who have RAS-wild type tumors with severe liver dysfunction due to multiple liver metastases; HAI is intended to have few side effects and has a high local control rate.

[A Case of Metastasis to the Base of the Skull after Rectal Cancer Operation with Symptom Management via Radiotherapy].

In 2009, A 67-year-old woman underwent high anterior resection for rectal cancer(RS, type 2, pT3, pN1, cM0, pStage III a). U FT/LV was administered for 6 months as adjuvant chemotherapy after the operation. Because peritoneum dissemination and pelvic lymph node metastasis developed 9 months after the operation, CapeOX plus Bmab therapy was started, and we monitored the cancer partial response for the next 6 years. Six years and 9 months after the operation, we detected metastasis to the sacrum; thus, radiotherapy was started. Seven years after the first operation, we detected pulmonary, liver, distant lymph node, and subcutaneous metastasis. Additionally, in the next month, she complained of double vision and dysarthria, and metastasis to the base of the skull was diagnosed via head MRI scanning. We started radiotherapy, and the symptoms gradually improved. Although we started IRIS plus Bmab therapy for pulmonary, liver, distant lymph node, and subcutaneous metastasis, it became a progressive disease(PD). She passed away 7 years and 6 months after the first operation. In this case, radiotherapy was useful for symptom management of metastasis to the base of the skull after surgery for rectal cancer, which is an extremely rare occurrence.

[Evaluation of Bevacizumab in Combination with Weekly Paclitaxel for Locally Advanced Breast Cancer].

Locally advanced breast cancer that exhibits bleeding, has a foul odor, and expresses an exudate often reduces the quality of life(QOL). Bevacizumab(Bv)in combination with weekly paclitaxel(PTX)therapy has a high response rate. To date, we have used this combination for 8 cases of locally advanced breast cancer in our hospital. The patients' mean age was 62.1 years. The tumors were T4b in 6 cases, T4c in 1 case and T4d in 1 case. The clinical stage was Stage III B in 1 case and Stage IV in 7 cases. The subtype was Luminal A in 2 cases, Luminal B in 4 cases, and triple negative in 2 cases. The mean dosage duration was 5.8 months. Five cases underwent local control operations after chemotherapy. One case showed a complete response, 4 cases had a partial response, 2 cases had a stable disease and 1 case had progressive disease. Four cases with Grade 2-3 hypertension and 4 cases with Grade 2 neutropenia were identified. Bvin combination with weekly PTX therapy had a high response rate, and 5 patients were able to undergo surgery. As QOL improved after treatment and the safety did not have any problem, Bv in combination with weekly PTX therapy is one of the effective treatments for locally advanced breast cancer.