[A Case Report of Metastatic Breast Cancer with Peritoneal Metastasis and Massive Ascites Responding to CDK4/6 Inhibitor(Palbociclib)].

A 52-year-old woman was presented with abdominal distension. Chest-abdominal CT showed some tumors in the left breast, enlarged axillary lymph nodes, ovary metastasis peritoneal thickening, a large amount of ascites. The diagnosis of needle biopsy in the breast mass was invasive ductal carcinoma, Luminal A type. The large amount of ascites decreased after the start of administration of fulvestrant and CDK4/6 inhibitor(PAL). Also chest and abdominal CT showed reduction of all lesions. We found the high expression of cyclin D1 protein and the negative of p16 protein in tissues of the needle biopsy. Fifty months later, she continues to do good ADL and PR status. We experienced a case of metastatic breast cancer with massive ascites and peritoneal metastasis that was successfully treated with a CDK4/6 inhibitor(PAL)and achieved long- term survival.

[A Case of Rectal Cancer Diagnosed Based on Brain Metastasis and Had a Long-Term Prognosis by Radical Resections].

The patient was a 57-year-old man who visited the department of neurosurgery for headache and lightheadedness. He was admitted with a diagnosis of brain tumor based on imaging findings. Severe brain dysfunction and mild ataxia were observed, and craniotomy tumor resection was performed 5 days after admission. He was diagnosed with brain metastasis of colorectal cancer based on histopathological examination and endoscopic findings, and was therefore referred to our department. No extracranial metastases were observed, laparoscopic-assisted low anterior resection was performed 1 month after the craniotomy. The final diagnosis was rectal cancer(Ra), pT3N0M1a(BRA), Stage Ⅳa. Three months after the craniotomy, subsequent MRI examination revealed a new metastatic lesion inferior to the tumor excision cavity, and gamma knife radiosurgery was performed. However, because an increasing tendency was noted, craniotomy was performed again 7 months after the first craniotomy. Following operative treatment, follow up has been performed without adjuvant chemotherapy or prophylactic irradiation, the patient has survived without recurrence at 34 months postoperatively. Here, we report a valuable rare case of solitary brain metastasis of colorectal cancer in which prognosis could be expected by radical resections.

Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma.

BACKGROUND: Despite reports of a link between human papillomavirus (HPV) infection and mechanistic target of rapamycin (mTOR) signaling activation, the role of the mTOR pathway, especially raptor and rictor, in HPV-related head and neck cancer is still unclear. The aim of the present study was to elucidate the role of the mTOR pathway in HPV-related oropharyngeal squamous cell carcinoma (OPSCC). METHODS: The present study involved two strategies. The first was to investigate the activity of mTOR and mTOR-related complexes in high-risk HPV-positive (UM-SCC47 and CaSki) and HPV-negative (SCC-4 and SAS) cancer cell lines. The second was to elucidate mTOR complex expression in 80 oropharyngeal cancer tissues and to examine the relationship between mTOR complex expression and survival in patients with OPSCC. RESULTS: The UM-SCC47 and CaSki cell lines showed high gene and protein expression of raptor. They also exhibited G1/S and G2/M phase cell cycle arrest following 24 h incubation with 6 µM temsirolimus, a rapamycin analog, and temsirolimus administration inhibited their growth. HPV-related OPSCC samples showed high gene and protein expression of raptor and rictor compared with HPV-unrelated OPSCC. In addition, HPV-related OPSCC patients with high raptor and rictor expression tended to have a worse prognosis than those with low or medium expression. CONCLUSIONS: These results suggest that raptor and rictor have important roles in HPV-related OPSCC and that temsirolimus is a potential therapeutic agent for patients with HPV-related OPSCC. This is the first report to reveal the overexpression of raptor and rictor in HPV-related OPSCC.

ERCC1 C8092A polymorphism predicts fair survival outcome in Japanese patients with pharyngo-laryngeal squamous cell carcinoma.

PURPOSE: To evaluate the prognostic significance of DNA excision repair gene polymorphisms, excision repair cross-complementation group 1 (ERCC1) and X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) polymorphisms were investigated in Japanese patients with head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 225 consecutive patients with HNSCC who underwent surgery or chemoradiotherapy/radiotherapy (CRT/RT) with curative intent as primary treatment from 2006 to 2017 were recruited. ERCC1 C8092A and XRCC1 Arg399Gln polymorphisms in DNA extracted from individual blood samples were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Cumulative survival was estimated by Kaplan-Meier analysis with a log-rank test and Cox proportional hazards model stratified by treatment arm, adjusting for clinical prognostic factors. RESULTS: Multivariate analysis showed that carriers with the ERCC1 8092 (C/A+A/A) genotype (hazard ratio, 3.56; 95% confidence interval, 1.22-7.39; p = 0.02) had significantly worse survival than those with ERCC1 8092 C/C who received CRT/RT. Conversely, the XRCC1 Arg399Gln polymorphism did not influence survival in patients who received CRT/RT as well as surgery. CONCLUSION: The ERCC1 C8092A polymorphism might be an independent predictor of response to CRT and survival outcome in patients with HNSCC. This is the first report to investigate the role of DNA excision repair gene polymorphisms in patients with head and neck cancer in a Japanese population.

[Conversion Therapy for HER2-Positive Metastatic Breast Cancer with Intrathoracic Lymph Node Metastasis].

A 42-year-old woman consulted our hospital with chief complaints of a right breast mass and pain. Based on needle biopsy of the breast tumor, the pathological diagnosis was invasive ductal carcinoma(scirrhous type), which tested positive for estrogen, progesterone, and HER2 receptor. PET-CT(FDG)showed intrathoracic lymph node metastasis. After several tests, she received a diagnosis of cT2N1M1(LYM), Stage Ⅳ breast cancer. She received pertuzumab, trastuzumab, and docetaxel treatments. After chemotherapy, the intrathoracic lymph node and breast tumors were not observed. She underwent mastectomy and axillary lymph node dissection. The pathological diagnosis showed a complete response after surgery. The patient's postoperative course was uneventful; she had received radiotherapy and anti-HER2 therapy. Twenty-three months after the surgery, no recurrence was observed. Herein, we report successful treatment of Stage Ⅳ breast cancer with conversion therapy.

[Assessment of Curative Resection in Patients with Multiple Relapses of Colorectal Cancer].

We assessed the therapeutic effect of curative resection in patients with multiple relapses of colorectal cancer using the time to surgical failure(TSF)as an index. We included 24 patients who experienced recurrence after curative resection of primary colorectal cancer at our department between 1993 and 2015. Curative resection for multiple relapses was possible in these patients. The sites of recurrence included the liver, lungs, peritoneum, lymph nodes, localized, and brain in 9, 8, 3, 3, 2, and 1 patients, respectively. The relapse occurred in 2 organs in 2 patients. The TSF after curative resection of recurrent lesions was 25.6 months, with a 5-year TSF-free rate of 40.2%. The clinicopathological factors associated with poor prognosis were age B65 years at the time of recurrence, absence of distal metastasis at primary onset, and only 2 curative resections for relapses. However, there was no difference in prognosis because of the number of twice recurrent lesions. Therefore, curative resection should be proactively performed as long as feasible in colorectal cancer patients with multiple lesions or multiple relapses.

[Examination of Prognosis and Adjuvant Chemotherapy in Stage â ¡ and Stage â ¢ Resected Colorectal Cancer in the 9th Edition Japanese Classification of Colorectal Carcinoma].

In the 9th edition Japanese Classification of Colorectal Carcinoma, Stage Ⅱ and Stage Ⅲ colorectal cancer(CRC)were subdivided by TNM classification on invasion and number of lymph node metastases. We studied prognostic comparison and relation of adjuvant chemotherapy at the new classification. We included 400 cases with resected Ⅱ and Ⅲ CRC from 2007 to 2014. Ⅱa/Ⅱb/Ⅱc/Ⅲa/Ⅲb/Ⅲc were 97/68/20/24/124/67 cases. Adjuvant chemotherapy was performed at 19/32/45/66/59/70% in Ⅱa/Ⅱb/Ⅱc/Ⅲa/Ⅲb/Ⅲc, with or without adjuvant chemotherapy at each stage survival rates were compared. In Ⅱa/Ⅱb/Ⅱc, DSS was 97/97/82% and DFS was 89/88/76%, and the prognosis of Ⅱc was significantly worse. In Ⅲa/Ⅲb/Ⅲc, DSS was 95/86/57% and DFS was 82/77/41%. By the presence or absence of adjuvant chemotherapy, significantly differences were obtained at Ⅲb and Ⅲc. Prognosis of Ⅱc was almost same as Ⅲb, and prognosis of Ⅲa was almost same as Ⅱb. Therefore, we considered adjuvant chemotherapy with oxaliplatin should be performed to Ⅱc, Ⅲb, and Ⅲc.

Staging and prognosis of oropharyngeal carcinoma according to the 8th Edition of the American Joint Committee on Cancer Staging Manual in human papillomavirus infection.

PURPOSE: The aim of this study was to evaluate the 8th edition of the American Joint Committee on Cancer Staging Manual: Head and Neck Section on oropharyngeal squamous cell cancer (OPSCC) and to clarify the relationship between p16 overexpression and the presence of human papillomavirus (HPV) DNA using fresh frozen samples. METHODS: Samples from 100 OPSCC patients were analyzed using polymerase chain reaction (PCR) and p16 immunohistochemistry. RESULTS: Five-year overall survival (OS) was 73.0%, 93.9%, and 62.2% in all, p16-positive (n = 34), and p16-negative (n = 66) cases, respectively. OS tended to be better aligned with stage in the 8th edition than in the 7th edition. The 5-year OS was 96.0% in never or light smokers (< 40 pack-years), and 87.5% in heavy smokers (≥ 40 pack-years) in the p16-positive group, respectively (p = 0.027). HPV infection was found in 100% of p16-positive and 21.2% of p16-negative cases. The p16-positive cases had higher viral load and integrated physical status than the p16-negative cases. Although 1 case with p16 overexpression showed no PCR amplification using consensus primers, PCR amplification was detected using HPV 16 E6-specific primers. CONCLUSIONS: The 8th edition predicts OPSCC prognosis more accurately than the 7th edition and p16-overexpression is an excellent surrogate marker for detecting HPV infection. Although high-risk-type HPV infection was observed in p16-negative cases, it showed no significant effect in survival outcome.

[A Case of Low-Grade Appendiceal Mucinous Neoplasm with Cecum Cancer].

The case was a 76-year-old man. He visited our hospital for a positive fecal occult blood test finding at a medical examination. A colonoscopy revealed a macroscopic, 30 mm, type-1 lesion in the cecum. We performed laparoscope-assisted ileocolic resection and D3 dissection, with a diagnosis of cecum cancer. In postoperative histopathological examination, the tumor in the cecum was diagnosed as a well-differentiated tubular adenocarcinoma. In addition, a low-grade appendiceal mucinous neoplasm(LAMN)was observed on the distal side of the appendix. The patient has survived for 9 months after surgery without recurrence. We report this case with a review of the literature.

[A Case of Lung Metastases from Rectal Cancer Treated for Quite Long with FOLFIRI plus Ramucirumab as a Late Line of Therapy].

We herein report a case of lung metastases from rectal cancer treated with FOLFIRI plus ramucirumab(Ram)therapy after salvage for a long time. A 44-year-old woman underwent low anterior resection for rectal cancer. Fifteen months after the surgery, mFOLFOX6 plus bevacizumab(BV)therapy was initiated for left obturator lymph node metastases. Although the target lesion shrunk, left lung metastasis was found 36 months after the surgery. Partial resection of the lung metastasis was performed, and carbon-ion radiotherapy for pelvic recurrence was administered. Following these treatments, mFOLFOX6 plus BV therapy was administered again for multiple lung metastases 42 months after the surgery. FOLFIRI plus BV therapy, TAS- 102 plus BV therapy, and regorafenib were then administered because of the disease progression. Although the best supportive care was provided after disease progression, FOLFIRI plus Ram therapy was initiated owing to the patient's wish. Although Grade 3 hematological toxicity was observed, severe digestive symptoms were not noted. Long-term administration(approximately 1 year, 21 courses)of the drugs was possible with withdrawal. The patient died due to disease progression 66 months after recurrence. We experienced a case in which FOLFIRI plus Ram therapy after salvage line could be administered for a quite long time. It has been suggested that anti-VEGF drugs with different targets may improve the prognosis even as a late line of therapy if it is tolerable.

[Impact of Postoperative Inflammatory Status on Colorectal Cancer Prognosis].

To clarify the prognostic impact of postoperative inflammatory status, serum CRP levels on POD3 after radical resection (POD3 CRP)were evaluated as an indicator of inflammatory response after surgery in patients with colorectal cancer. Of the colorectal cancer patients who underwent radical resection at our department between 2000 and 2015, 916 patients with Stage Ⅰto Ⅳdisease were included in the analyses. The patients were divided into 2 groups according to high and low POD3 CRP levels. The POD3 CRP levels of the patients were analyzed for the 75th percentile that was 12.16mg/dL(range, 0.06- 33.78). The cancer-specific 5-year survival rate was 80.6%in patients in the high group and 90.5%in those in the low group, indicating poor prognosis in patients with high values. POD3 CRP levels were an independent prognostic factor in the multivariate analysis. It was suggested that the degree of inflammation after surgery influences the postoperative prognosis after radical resection for colorectal cancer.

[Efficacy of Negative Pressure Wound Therapy for Post-Operative Wound Dehiscence after Resection of a Metastatic AbdominalWal lTumor from Cecal Cancer during Chemotherapy with Bevacizumab].

A 74-year-old man with recurrence of cecal cancer received systemic chemotherapy(CapeOX plus bevacizumab). After the administration of 9 courses, he reported sudden appearance of bloody bowel discharge. Endoscopic examination could not locate the bleeding point. A CT scan indicated that the small intestine was affected by the recurrence of cancer. Therefore, resection of the small intestine was performed after 6 weeks of drug withdrawal. Although direct closure with fascia incision was performed for the repair of wound dehiscence after surgery, re-dehiscence occurred because of paralytic ileus. Wound lavage and nutritional intervention were performed, followed by negative pressure wound therapy. Excellent wound healing was achieved by this therapeutic approach for 3 months.

[Efficacy of Laparoscopic Surgery for Elderly Patients with Colorectal Cancer Over 80 Years Old].

The efficacy of laparoscopic surgery for elderly patients aged over 80 years who have colorectal cancer was investigated concerning complications. Sixty-five patients over 80 years old who underwent colorectal cancer resection until January 2018 were enrolled. Factors that led to complication were analyzed retrospectively. Thirty-three men and 32 women were included, with a median age of 83 years. Forty-eight cases were located at the colon; and 17, at the rectum. The median operating time was 164 minutes, including 39 cases treated with the laparoscopic approach. Postoperative complications were observed in 28 cases(43.1%), of which 15(23.1%)had a Clavien-Dindo(CD)classification of Grade BⅡ. These cases had significantly prolonged postoperative hospital stay. Complications included 10 cases of incisional surgical site infection(SSI), 9 cases of ileus, 6 cases of melena, 2 cases of urinary infection, 2 cases of urinary disorder, and 1 case of postoperative death. Open surgery was the only significant factor associated with the incidence of CD classification of BⅡ(p=0.0330). Among the complications, the incisional SSI was reduced by laparoscopic surgery(p=0.0050). The number of laparoscopic surgeries reduced the incidence of CD classification BⅡ of complications in elderly patients aged over 80 years who had with colorectal cancer resection. The use of incisional SSI also decreased with the use of laparoscopic surgery. Laparoscopic surgery for colorectal cancer in elderly patients may lead to reduced complication rates.

[Prognostic Relevance of Palliative Tumor Resection and Chemotherapy in Stage â £Unresectable Colorectal Cancer].

This study was conducted to evaluate the prognostic factors in patients with unresectable Stage Ⅳ colorectal cancer. One hundred and twenty-five patients who underwent either primary resection or chemotherapy for unresectable Stage Ⅳ colorectal cancer and were treated at our hospital between April 2004 and March 2014 were enrolled this study. In multiple univariate analysis, the overall survival(OS)was significantly longer in the palliative resection and chemotherapy groups. Upon dividing the 125 patients in 3 groups(the intensive chemotherapy group[L-OHP or CPT-11 regimen], extensive chemotherapy group[other regimen], and non-chemotherapy group), the intensive chemotherapy group showed significantly longer OS. Next, upon comparing the patients based on the treatment they received(surgery plus chemotherapy, surgery alone, and chemotherapy alone), the surgery plus chemotherapy group showed longer OS. With both studies combined as 5 groups, only the surgery plus intensive chemotherapy group showed longer OS. This is shown in unresectable Stage Ⅳ cancer patients, wherein resection of the primary lesion in addition to intensive chemotherapy contributes to longer OS.

[Treatment Outcomes of Curative Resection for Colorectal Cancer with Synchronous Liver Metastasis].

The aim of this study was to clarify prognosis for curative resection performed for cases of colorectal cancer with synchronous liver metastasis and to use the findings as future treatment indices. Subjects comprised 61 patients who underwent curative resection at our hospital for colorectal cancer accompanied by synchronous liver metastasis between 1996 and 2014. The degree of liver metastasis was H1 for 47 cases and H2 for 14 cases. The Grade of liver metastasis was A for 29 cases, B for 18 cases, and C for 14 cases. Liver resection was performed simultaneously with that of the primary lesion for 33 cases, and after that of the primary lesion for 28 cases. The post-curative resection survival period was 58.0 months, and the 5-year survival rate was 49.9%. In terms of the relationship between prognosis and clinicopathological factors, prognosis was found to be poor when the wall depth of the primary lesion was pT4 and when the liver metastasis Grade was B or C. Meanwhile, prognosis did not differ depending on the timing of liver metastasis resection, whether chemotherapy was performed after liver resection, and whether curative resection was performed for initial occurrence only or recurrence resection was performed. The results indicated that for cases of colorectal cancer with synchronous liver metastasis, primary lesion wall depth and liver metastasis Grade were prognostic factors, and that the treatment strategy did not necessarily have to consider resection timing.

B-Type Natriuretic Peptide in Heart Failure With Preserved Ejection Fraction　- Relevance to Age-Related Left Ventricular Modeling in Japanese.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) is increasing with aging of the population. Plasma levels of B-type natriuretic peptide (BNP) increase in proportion to the severity of left ventricular (LV) dysfunction. The object of this study was to examine the plasma levels of BNP in HFpEF to better understand the pathogenesis of HFpEF as compared with HF with reduced EF (HFrEF).Methods and Results:The study subjects comprised 468 HFpEF patients (158 men, 310 women, mean age 81.3±9.6 years) and 126 HFrEF patients (77 men, 49 women, mean age 75.4±12.0 years) who underwent echocardiography and routine clinical examinations including plasma BNP. Age, female prevalence, systolic blood pressure and pulse pressure were higher in the HFpEF patients than in the HFrEF patients (P<0.0001, P<0.001, P<0.0001, and P<0.0001, respectively). Plasma BNP levels, LV diastolic dimensions, and LV mass index (LVMI) were lower (P<0.0001, P<0.0001, and P<0.0001, respectively), while relative wall thickness was higher (P<0.0001) in the HFpEF patients than in the HFrEF patients. Multiple regression analysis revealed that LVMI, EF, plasma levels of albumin, C-reactive protein, and uric acid were the predictors of BNP levels (P<0.001, P<0.001, P=0.009, P=0.012, and P=0.018, respectively). CONCLUSIONS: Plasma BNP levels were lower and related to aging-related LV concentric remodeling/hypertrophy in HFpEF patients as compared with HFrEF patients, who were associated predominantly with eccentric LV hypertrophy.

Bite Wounds Caused by a Wild Boar: A Case Report.

A 74-year-old man was attacked by a wild boar while on his way home from his farm in the daytime in winter 2017 on the rural Izu peninsula. He did not provoke the boar; however, hunters were hunting animals in the mountains near the farm around the same time. The boar bit his left leg, and the man fell to the ground. The boar continued biting the man's left leg, and the man delivered a few kicks to the boar's face with his right leg. The boar then bit his right foot and ran away. The man was taken to a hospital, and a physical examination revealed 3 bite wounds on his left leg and right foot. The wounds were irrigated with sterilized saline and closed with sutures under local anesthesia. He received antibiotics and a tetanus toxoid booster. The next day, his wounds were found to be infected, and pus was drained from them. After these treatments, his wounds healed successfully. Animal bite wounds are frequently contaminated. Accordingly, in addition to early proper wound treatment, close observation of the wound is required for both the early detection of any signs of infection and early medical intervention, including appropriate drainage of pus and irrigation as necessary.

Two cases of compartment syndrome of the lower extremities during surgery for gynecological malignancies.

Two cases of compartment syndrome of the lower extremities occurring during surgery for gynecological malignancies are reported. In addition to the risk from being in the lithotomy position for over 4 h, these two cases were believed to have been caused by the combined use of a disposable wound retractor and abdominal retractors to secure the operative field. This conclusion is based on the fact that an abrupt increase in partial pressure of end-tidal CO2 (ETCO2) was observed when wound drapes and abdominal retractors were removed approximately 4 h after the start of surgery. Prolonged compression of the external iliac vein by a disposable wound retractor and abdominal retractors is believed to have induced congestion of the lower extremities, eventually resulting in compartment syndrome. To verify this, during subsequent surgeries of the same type, changes in the diameters of femoral arteries and veins when a disposable wound retractor and abdominal retractors were used were monitored using an ultrasound device, and the findings confirmed that changes in vascular diameter do occur.

[Maxillary Cancer with Metastasis to the Rouviere Nodes -- Complete Response to Chemoradiotherapy Using a Selective Intra-Arterial Infusion Technique].

We report a case of advanced maxillary cancer with multiple lymph node metastases, including metastasis to the Rouviere nodes, which were successfully treated with chemoradiotherapy using a selective intra-arterial infusion technique.A 71-yearold man presented to our hospital with complaints of a staggering gait and epistaxis.He was diagnosed with maxillary cancer (squamous cell carcinoma)classified as T4a disease.Because multiple lymph node metastases were detected, including metastasis to the Rouviere nodes, radical surgical treatment was considered inadequate.Thus, the patient was treated with concurrent chemoradiotherapy with selective intra-arterial infusion of nedaplatin and docetaxel.After chemoradiotherapy, the maxillary cancer and lymph metastasis nearly resolved and the patient achieved a complete response.No additional surgery was needed, and the patient was discharged.We suggest that chemoradiotherapy using a selective intra-arterial infusion technique is a highly effective treatment option for patients with maxillary cancer and metastasis to the Rouviere nodes.

[Significance of Perioperative Neutrophil Lymphocyte Ratio(NLR)in Gastric Cancer and Colon Cancer].

BACKGROUND: We examined the significance of neutrophil lymphocyte ratio(NLR)in gastric cancer and colon cancer in the perioperative period. METHOD: There were 46 patients(21 with gastric cancer and 25 with colon cancer). We examined the association between preoperative NLR and other indicators of nutritional status, as well as the relationship between preoperative NLR and the incidence of postoperative complications(all complications/infectious complications). RESULT: NLR was higher in those with zinc<65 mg, prognostic nutritional index(PNI)≤40, and modified Glasgow prognostic score(mGPS)of 2 (p<0.05). NLR showed no difference among all patients with complications(12 cases), but was higher in patients with infectious complications(p<0.05). CONCLUSION: Preoperative NLR is correlated with PNI as a predictor of infectious complications.