Pancreatic Adenosquamous Carcinoma: Experience Within an Integrated Health Care System.

Introduction Adenosquamous carcinoma (ASC) of the pancreas is a rare form of pancreatic cancer with a worse prognosis than pancreatic ductal adenocarcinoma. The authors report on a retrospective study of 13 patients diagnosed with ASC in an integrated health care system. Methods A retrospective review was performed of all patients with pancreatic cancer identified between February 2010 and December 2018. Twenty-three patients were diagnosed with pancreatic ASC. Patient demographics, tumor characteristics, treatment modalities, and median survival were evaluated. Results Median overall survival was 8 months (standard devision [SD] = 18.6). Eight out of 13 patients who received surgery upfront had a positive surgical margin (62%). Eleven patients received adjuvant therapy. Median survival for patients who received multimodal treatment was 57 months (SD = 5.7) compared with 2.5 months for patients who received only surgery. Median survival for patients with negative pathologic margins was 17 months (SD = 23.6). One patient was receiving neoadjuvant chemotherapy (6 months into treatment without any evidence of metastatic disease). Discussion The high proportion of positive surgical margins and large tumor size upon presentation suggest that primary tumor downstaging should be considered. The positive results from recent prospective trials on neoadjuvant chemoradiation for pancreatic ductal adenocarcinoma could be a promising foundation of information for the treatment of ASC. Conclusion ASC of the pancreas is an extremely aggressive malignancy with poor prognosis. Further work is needed to determine the optimal multimodal treatment regimen.

The best postoperative adjuvant therapy for patients with early stage cervical adenosquamous carcinoma.

BACKGROUND: Cervical adenosquamous carcinoma (ASC) was previously thought to be a subtype of cervical adenocarcinoma, but recent studies have found that the clinical features of the two diseases are different. Moreover, the pathological characteristics, survival, prognosis, and optimal ASC therapy remain unknown. This study aims to retrospectively analyze the postoperative survival of patients with early-stage ASC and to evaluate their condition after treatment with postoperative concurrent chemoradiotherapy (CCRT) and prophylactic irradiation of the para-aortic lymphatic drainage area. METHODS: This study enrolled 131 patients with pathologically confirmed ASC screened from 3502 patients with confirmed stage I-II cervical cancer diagnosis who had completed surgical treatments in our hospital. Among the 131 enrolled patients, 75 patients received CCRT, 33 patients received chemotherapy (CT), and 23 patients did not receive adjuvant treatment (named surgery alone (S alone). Of the 75 patients CCRT, 43 patients received prophylactic irradiation of the para-aortic lymphatic drainage area. The efficacy of the postoperative treatments of patients among groups (CCRT, CT, and S alone) was compared. RESULTS: The median follow-up time, age, and overall survival (OS) were 76 months, 43 years, and 74 months, respectively. The 3- and 5-year survival rates were 82% and 71.4%, respectively. The median disease-free survival (DFS) was 64 months. Cox regression analysis showed that postoperative adjuvant treatment modalities and positive lymph node metastases were associated with OS and DFS. Patients who received CCRT treatment had higher OS and DFS than those with CT and S alone. Prophylactic irradiation of the para-aortic lymphatic drainage area did not improve the OS and DFS of patients with CCRT treatment. However, further subgroup analysis suggested that it might improve survival rates in patients who had positive pelvic lymph nodes as confirmed by postoperative pathology. CONCLUSION: Postoperative CCRT improved the survival rates in patients with early-stage ASC. The value of prophylactic irradiation of the para-aortic lymphatic drainage area remains debatable, but it may benefit patients with pelvic lymph node involvement.

Gastric adenocarcinoma at stage IV with complete remission after neoadjuvant therapy concurrent with adenosquamous carcinoma of the ampulla of Vater: a case report and literature review.

BACKGROUND: Adenosquamous carcinoma (ASC) of the ampulla of Vater (AmV) is exceedingly rare with more aggressive behavior and worse prognosis than adenocarcinoma. The finding of ASC at the AmV in combination to the gastric adenocarcinoma has never been reported in the literature before. CASE PRESENTATION: An old lady was diagnosed as gastric adenocarcinoma at stage IV with enlargement of supraclavicular lymph nodes by gastroscopy and histopathological evaluation 3 years ago. Afterwards, the patient achieved complete remission after regular chemotherapy. However, the patient manifested yellow sclera and skin, choluria and clay colored stool 3 months ago. Preoperative contrast-enhanced CT, ERCP, MRCP, and PET/CT revealed the presence of an ampullary tumor. The patient then underwent laparoscopic radical gastrectomy and pancreaticoduodenectomy with regional lymph node dissection. Postoperative cytological analyses confirmed the diagnosis of gastric ulcer with complete response to neoadjuvant therapy and ASC at the AmV. The patient's postoperative outcome was uneventful. CONCLUSION: Drawing firm conclusions about the diagnosis of ampullary ASC is difficult because of the difficulty in acquiring both adenocarcinoma and SCC components by fine needle biopsy. The rarity of ASC of the AmV coexistent with gastric carcinoma makes it difficult to elucidate their clinicopathological characteristics, therapeutic strategies and overall prognosis. Surgical resection still remains the main treatment method.

Glassy cell carcinoma of the uterine cervix: 20-year experience from a comprehensive cancer center.

PURPOSE: Glassy cell carcinoma (GCC) of the uterine cervix is a rare entity. This study aims at describing the clinical characteristics and outcomes of cervical GCC patients treated in a comprehensive cancer center. MATERIAL AND METHODS: We retrospectively reported patients and tumors characteristics, therapeutic management, overall survival (OS), progression-free progression (PFS), relapse rates, and toxicities. RESULTS: Between 1994 and 2014, 55 patients were treated with curative intent. The median age at diagnosis was 41 years (range, 20-68). Among 22 patients with early stage tumors (IA2-IB1-IIA1), 17 had preoperative brachytherapy, followed by radical hysterectomy. Among 33 patients with locally advanced disease (≥IB2), 32 underwent chemoradiation±brachytherapy boost. After a median follow-up of 5.4 years (range, 0.15-21.7 years), 18/55 (33%) patients experienced tumor relapse. Local recurrence occurred in 2/22 (9%) patients with early disease (treated with upfront surgery) and in 3/32 (9%) patients with locally advanced disease. Most frequent relapses were distant, occurring in a total of 11/55 patients (20%). PFS rates at 5-year were 86.4% (95% CI: 63.4-95.4) for early stage versus 75.9% (95% CI: 55.2-89.2) for locally advanced stages, respectively (P=0.18). CONCLUSION: Large cohort data are warranted to guide the optimal management of GCC. From this retrospective analysis, a multimodal approach yielded to good disease control in early stages tumors. Given the high-risk of distant failure, consideration should be given to adjuvant chemotherapy in locally advanced disease.

Complementary surgery for cervical cancer patients inadequately treated with extrafacial hysterectomy.

OBJECTIVE: To evaluate surgical outcomes and survival outcomes of cervical cancer patients who underwent complementary surgery after an extrafacial hysterectomy METHODS: Patients with cervical cancer, who underwent extrafacial hysterectomy initially and thereafter underwent complementary surgery were reviewed retrospectively. Complementary surgery consisted of radical parametrectomy, proximal vaginectomy and pelvic lymphadenectomy. RESULTS: Twenty patients were evaluated. Histopathologic subtype was squamous cell carcinoma in twelve patients, adenocarcinoma in six patients and adenosquamous carcinoma in two patients. Route of surgery was laparotomy in 19 patients and laparoscopy in one patient. Two patients were staged as stage 1A2, nine were staged as stage 1B1, four were staged as stage 1B2, one was staged as stage 2A1, one was staged as stage 2B and three were staged as stage 3C1. The median tumor size was 16.5 (Range, 4-40) mm. Grade ≥ 3 complications related to surgery occured in 8 (40%) patients. Four of them were managed intraoperatively and recovered problem free. Remaining four (20%) needed reoperation. Pathology reports revealed involvement of parametrium in one (5%) patient, involvement of the proximal vagina in one (5%) patient, matastasis to pelvic lymph nodes in 3 (15%) patients. Five (25%) patients received adjuvant radiotherapy. Consequently, 5-year and 10-year cumulative survival was calculated as 94%. CONCLUSION: Complementary surgery and radiotherapy show similar oncologic outcomes in patients with early-stage cervical cancer who had undergone simple hysterectomy initially. Complementary surgery is associated with slightly higher rate of morbidity compared with radiotherapy, however significant proportion of complications can be noticed and repaired intraoperatively.

Pattern of recurrence in patients with endometrial cancer: A retrospective study.

INTRODUCTION: Endometrial cancer (EC) known prognostic factors are not sufficient to predict either outcome or recurrence rate/site: to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for a more tailored adjuvant treatment and follow-up schedule. METHODS: 758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and highrisk HR) and surgically treated as recommended, followed by adjuvants therapies when appropriate. RESULTS: Higher recurrence rate (RR) was significantly detected (p < 0,001) in the HR group (40,3%) compared to LR (9,6%), IR (16,7%) and I-HR (17,1%). Recurrences were detected more frequently at distant sites (64%) compared to pelvic (25,3%) and lymph nodes (10,7%) recurrences (p < 0,0001): only in LR group, no differences were detected between local and distant recurrences. 5-Year distant-free (LR 99%, IR 94%,I-HR 86%, HR 88%) and local-free survivals (LR 99%, IR 100%,I-HR 98%, HR 95%) significantly differ between groups (p < 0,0001 and p = 0,003, respectively). Adjuvant therapy modifies RRs only in LR group (p = 0,01). CONCLUSION: To identify biological factors to stratify patients at higher risk of relapse is needed. Distant site relapse could be the main reason of endometrial cancer failure follow-up, independently or in addition to their risk class prognosis.

TAS-118 (S-1 plus leucovorin) versus S-1 in patients with gemcitabine-refractory advanced pancreatic cancer: a randomised, open-label, phase 3 study (GRAPE trial).

BACKGROUND: In our previous randomised phase 2 study for patients with gemcitabine-refractory advanced pancreatic cancer, S-1 plus leucovorin improved progression-free survival compared with S-1 alone. Here, we evaluated the efficacy of TAS-118 (S-1 plus leucovorin) versus S-1 in overall survival (OS). PATIENTS AND METHODS: This randomised, open-label, phase 3 study was conducted at 58 centres in Japan and Korea. Patients with metastatic pancreatic cancer that progressed during first-line gemcitabine-based chemotherapy or recurred during or after post-operative gemcitabine-based adjuvant treatment were randomly assigned (1:1) to receive either S-1 (40-60 mg, twice daily for 4 weeks in a 6-week cycle) or TAS-118 (S-1 40-60 mg plus leucovorin 25 mg, twice daily for 1 week in a 2-week cycle). The primary end-point was OS. RESULTS: A total of 603 patients were randomised, and 300 and 301 patients received TAS-118 and S-1, respectively. There was no difference in OS between groups (median OS for TAS-118 versus S-1, 7.6 months versus 7.9 months; hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.82-1.16]; P = 0.756). Progression-free survival was significantly longer with TAS-118 than S-1 (median, 3.9 months versus 2.8 months; HR, 0.80 [95% CI, 0.67-0.95]; P = 0.009). There were interactions between Japan and Korea (P = 0.004) and between unresectable and recurrent disease (P = 0.025) in OS. Incidence, profile and severity of adverse events were similar between groups. CONCLUSION: TAS-118 did not improve OS in patients with gemcitabine-refractory advanced pancreatic cancer compared to S-1. Further studies are needed to find patients who have benefit from adding leucovorin to S-1.

Combined Treatment with Autologous CIK Cells, Radiotherapy and Chemotherapy in Advanced Cervical Cancer.

To investigate the clinical efficacy of autologous cytokine induced killer (CIK) cells transfusion combined with radiochemotherapy in the treatment of advanced cervical cancer. A total of 89 hospitalized patients with advanced cervical cancer were admitted and divided into the treatment group (44 cases, autologous CIK cells transfusion combined with radiochemotherapy) and the control group (45 cases, radiochemotherapy) by a randomized non-blind method. Comparisons of therapeutic efficacies, immune functions, life qualities and survival rates were analyzed between the two groups. The short-term therapeutic efficacy of the treatment group was significantly higher than that of the control group. There was no significant difference in 1, 2 and 3 year survival rates between the two groups. Compared with pre-treatment, levels of CD3+, CD4+/CD8+ in peripheral blood were increased in the CIK group, which were reduced in the control group. In the CIK group,only the feeling was depressed on the 25th day post-treatment (T25) compared with the day before treatment (B1). However in the control group, the function of body, role, social and holistic health was obvious disordered on day T25 compared with day B1. On day T25, there were significant differences in function of body, social and holistic health between two groups. Autologous CIK cells transfusion combined with radiochemotherapy shows better short-term efficacy than radiochemotherapy alone in the treatment of advanced cervical cancer, which obviously improves immune function and life quality of patients with low side effects.

Treatment outcomes of locally advanced cervical cancer by histopathological types in a single institution: A propensity score matching study.

BACKGROUND: In the current National Comprehensive Cancer Network (NCCN) guidelines, the standard treatment methods revealed no difference between locally advanced cervical (LAC) adenocarcinoma/adenosquamous carcinoma (AC/ASC) and LAC squamous cell carcinoma (SCC). The aim of this study was to compare the treatment outcomes of LAC AC/ASC with LAC SCC through the propensity score matching (PSM) analysis. METHODS: This retrospective study enrolled 181 LAC cancer patients who were treated with intensity modulated radiotherapy/volumetric modulated arc therapy and concurrent weekly cisplatin 30-40 mg/m2. In total, there were 151 LAC SCC patients and 30 LAC AC/ASC patients. The endpoints were overall survival (OS), disease-free survival (DFS), locoregional failure-free survival (LRFFS), and distant metastasis-free survival (DMFS). A 1:1 ratio PSM analysis was performed using the nearest neighbor method with a caliper of 0.20. Treatment outcomes were compared between 30 matched LAC SCC patients and 30 LAC AC/ASC patients. RESULTS: Before a 1:1 ratio PSM, the 5-year OS, DFS, LRFFS, and DMFS in the LAC SCC group were 78.6%, 71.3%, 88.2%, and 76.2%, respectively. After a 1:1 ratio PSM, the 5-year OS, DFS, LRFFS, and DMFS in the LAC AC/ASC group were 46.0%, 43.3%, 70.0%, and 45.4%, respectively, which were all significantly inferior than the rates of 90.0%, 75.8%, 96.6%, and 78.8% in the matched LAC SCC group, respectively (p < 0.05). CONCLUSION: LAC AC/ASC carries a poorer prognosis than LAC SCC. LAC AC/ASC needs more aggressive treatment in order to achieve higher OS and DFS.

Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer.

Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.

Distance from a Comprehensive Cancer Center: A proxy for poor cervical cancer outcomes?

OBJECTIVE: To evaluate the potential relationship between outcomes in cervical cancer patients based on distance from our Comprehensive Cancer Center (CCC). METHODS: A retrospective cohort study of cervical cancer patients was performed. Abstracted data included: demographics, clinicopathologic variables, treatment, and survival. Analyses both by quartiles and distance <100 and ≥100miles from our institution were performed. Data were analyzed using SAS version 9.2. RESULTS: 390 patients living a median distance of 58.1miles (range 1.2-571miles) from our CCC were identified. Patients were generally white (n=249), non-smokers (n=226), with Stage IB disease (n=222), squamous histology (n=295) and underwent primary surgical therapy (n=229). Patients were divided into both quartiles as well as two strata: <100 and ≥100miles for comparison. Progression-free survival (PFS) and overall survival (OS) favored patients living closer to our center with a lower median OS for patients living ≥100miles (65.4vs. 99.4months; p=0.040). Cox proportional hazard modeling noted that advanced stage was predictive of inferior PFS and OS, while other clinical covariates including age, BMI, race, smoking status and histology had a variable impact on outcomes and distance >100miles was associated with a higher risk of death (hazard ratio [HR]=1.68, 95% confidence interval [CI] 1.11-2.54). CONCLUSION: Overall survival for patients living >100miles from our CCC was worse when compared to patients in closer proximity. Outreach efforts and utilization of navigators may help decrease the impact of geographic and racial disparities on outcomes.

Effects of Neoadjuvant Chemotherapy Plus Radical Surgery as Front Line Treatment Strategy in Patients Affected by FIGO Stage III Cervical Cancer.

BACKGROUND: To assess the clinical efficacy and prognostic outcome of neoadjuvant chemotherapy (NACT) plus radical surgery (RS) as front line treatment in patients with FIGO stage III cervical cancer (CC). METHODS: In this retrospective study, 52 FIGO stage III CC patients treated from 2005 to 2015 were included. All patients received platinum-based chemotherapy. Patients reporting clinical response or stable disease after NACT underwent to RS and bilateral systematic pelvic lymphadenectomy with or without aortic lymphadenectomy or anterior exenteration. Patients with progressive disease underwent palliative management. RESULTS: After NACT, clinical response was observed in 23 patients (44 %): 4 (7.7 %) complete and 19 (36.5 %) partial responses, respectively. Also, 15 patients (28.8 %) had stable disease and 14 (26.9 %) showed disease progression. RS was performed in 40 cases (76.9 %): respectively, 28 (70 %) and 7 (17.5 %) underwent type C2 and D radical hysterectomy, while 5 patients (12.5 %) underwent anterior exenteration. At pathological evaluation, 23 patients (57.5 %) had positive pelvic nodes and 4 (10 %) also had positive aortic nodes. In 6 patients (15 %), moderate-severe (G3-G5) complications occurred. A total of 27 patients (67.5 %) received adjuvant therapy: 16 patients (40 %) received chemotherapy, 10 (25 %) received chemoradiation and 1 (2.5 %) received radiotherapy. Disease relapse occurred in 24 cases (60 %). After follow-up period of 60 months, the median OS of the whole population included was 37 months. Among the 40 surgically treated patients, median OS and DFS were 48 and 23 months, respectively. CONCLUSIONS: NACT plus RS represent a valid alternative with acceptable morbidity for patients with stage III CC.

Serum carbohydrate antigen 12-5 level enhances the prognostic value in primary adenosquamous carcinoma of the lung: a two-institutional experience.

OBJECTIVES: Primary adenosquamous carcinoma (ASC) of the lung is rare. The current study was a retrospective two-institutional analysis of surgical therapy with respect to the clinicopathological characteristics and prognostic factors associated with ASC of the lung. METHODS: The clinical records of patients with pathologically confirmed ASC of the lung treated surgically in two centres between January 2008 and December 2014 were retrospectively reviewed. RESULTS: One hundred and four patients with ASC of the lung after surgical intervention, including 68 males and 36 females were identified. The 5-year overall survival (OS) and disease-free survival (DFS) of all ASC stages were 38.3 and 16.9%, respectively. Patients with N0, N1 and N2 ASC [N0 vs N1 (P = 0.047) and N1 vs N2 (P = 0.028), respectively], or Stage I, II and IIIA ASC [Stage I vs Stage II (P = 0.005) and Stage II vs Stage IIIA (P = 0.016), respectively] had significant differences with respect to OS. Multivariate analysis using a Cox proportional hazards model indicated that the level of serum carbohydrate antigen 12-5 (CA 12-5) (normal vs high level, P = 0.029), TNM stage [Stage I vs Stage IIIA (P < 0.001), Stage II vs Stage IIIA (P = 0.001)] and adjuvant chemotherapy (P = 0.027) were significant factors associated with OS in ASC patients, and TNM stage [Stage I vs Stage IIIA (P < 0.001), Stage II vs Stage IIIA (P = 0.003)] and adjuvant chemotherapy (P < 0.001) were the significant prognostic variables for DFS. CONCLUSIONS: Serum CA 12-5 level and TNM status predict the long-term prognosis of resected primary ASC of the lung. Postoperative platinum-based chemotherapy improved survival in patients with ASC.

Variations in survival and perioperative complications between hospitals based on data from two phase III clinical trials for oesophageal cancer.

BACKGROUND: Variations in institutional practice may contribute to different outcomes of cancer treatment. The impact of interinstitutional heterogeneity on outcomes between hospitals after oesophagectomy has not been examined previously using data from surgical clinical trials. METHODS: The data from two phase III trials for oesophageal cancer were used. Japan Clinical Oncology Group (JCOG) 9204 involved oesophagectomy (92-OP) versus oesophagectomy plus postoperative chemotherapy (92-POST), with accrual from 1992 to 1997. JCOG9907 involved postoperative chemotherapy (99-POST) versus preoperative chemotherapy (99-PRE), with accrual from 2000 to 2006. Hospitals contributing fewer than three patients were excluded. The influence of time and preoperative chemotherapy on interinstitutional heterogeneity related to postoperative complications and 5-year overall survival were evaluated by comparisons within and between these trial groups. Heterogeneity was estimated by a mixed-effects model after adjusting for age, sex, performance status, location of the primary tumour and clinical stage. RESULTS: Twelve hospitals in 92-OP (114 patients), 13 in 92-POST (114), 19 in 99-POST (158) and 18 in 99-PRE (154) were eligible. There was considerable heterogeneity in predicted postoperative complications in both groups in JCOG9204 (median 31.3 (range 15.0-68.2) per cent), and in 99-PRE (35.2 (22.6-46.6) per cent) but not in 99-POST (27.7 (27.7-27.7) per cent) from JCOG9907. A similar pattern was seen for predicted overall survival (92-POST: 66.4 (range 64.1-68.9) per cent; 99-PRE: 55.9 (54.0-59.7) per cent; 99-POST: 44.4 (44.4-44.4) per cent). CONCLUSION: Interinstitutional heterogeneity regarding complications and survival after oesophagectomy is a problem that merits wider consideration.

Trimodality therapy and definitive chemoradiotherapy for esophageal cancer: a single-center experience and review of the literature.

In the UK, the standard of care for esophageal cancer has generally combined surgery with neoadjuvant chemotherapy, with definitive chemoradiotherapy (dCRT) being reserved for certain subgroups. Chemoradiotherapy followed by surgery (trimodality therapy) has not been widely adopted. The outcomes of patients undergoing dCRT or trimodality therapy at our cancer center between 2004 and 2012 were restrospectively analyzed. Trimodality therapy was offered to selected patients of good performance status (World Health Organisation performance status 0/1), with squamous cell carcinoma or bulky adenocarcinoma. dCRT was offered to patients of good PS but with comorbidities, upper third tumors or at patient's request. Patients received four cycles of chemotherapy with a platinum agent (mostly cisplatin) and a fluoropyrimidine (mostly 5-fluorouracil) over a total of 11 weeks. Cycles 3 and 4 were given concurrently with radiotherapy: 50 Gy in 25 fractions for dCRT and 45 Gy in 25 fractions in the trimodality group. Surgery occurred 8-10 weeks following the completion of chemoradiotherapy. The cut-off length for maximum gross tumor volume length was 10 cm. One hundred two patients were included (47 received dCRT, and 55 received trimodality treatment). The majority of tumors were stage III (80.4%), and two-thirds were located in the distal esophagus (64.7%). Median follow-up was 44 months. The 2-year overall survival (OS) was 57.3% (median OS 39.7 months) for the dCRT group and 77.8% (median not reached) for the trimodality group. The 5-year OS rates were 38% and 58%, respectively. Postoperative mortality rate was low at 1.8%, and the pathological complete response rate was 23.6%. In conclusion, trimodality treatment for patients with esophageal and junctional gastroesophageal tumors offers high rates of 2-year survival, and the potential for long-term cure. dCRT is an established alternative for patients that are not fit or suitable for surgery.

Is there a place for sentinel technique in treatment of vaginal cancer?: feasibility, clinical experience, and results.

OBJECTIVE: To evaluate the clinical feasibility of sentinel lymph node (SLN) technique and the role of single-photon emission computed tomography with CT (SPECT/CT) compared to lymphoscintigraphy for detection of SLN in vaginal cancer. METHODS: The study was performed in a prospective, unicentric setting. Patients with vaginal carcinoma were scheduled for surgery and SLN labeling by peritumoral injection of 10-MBq technetium Tc 99m nanocolloid and patent blue. After 30 minutes, lymphoscintigraphy and SPECT/CT were carried out. We evaluated the number of SLNs in lymphoscintigraphy, SPECT/CT, and intraoperative histology of SLN and non-SLN as well as the impact of these results to therapeutic approach. RESULTS: Between January 2009 and December 2012, the SLN technique was used for 7 of 11 patients treated due to vaginal cancer. Detection rate was 100% (7/7). Lymphoscintigraphy and SPECT/CT showed at least one SLN in each patient. Lymphoscintigraphy detected 2.6 SLNs (range, 2-4 SLNs) per patient compared to 4.3 SLNs (range, 2-8 SLNs) in SPECT/CT (P = 0.053). Sentinel lymph nodes were detected in all patients during surgery with a mean number of 4.3 (range, 1-5). Pelvic SLNs were detected in all 6 patients with infiltration of middle or proximal vaginal third (100%). If the distal vaginal third was additional (3/7 patients) or exclusively (1/7 patients) infiltrated, the inguinal SLN detection rate was 33% and 100%, respectively. All patients with nodal metastases had at least one SLN positive for tumor. There were no false negatives. In 2 (29%) of 7 patients, treatment approach was modified owing to affected SLN. CONCLUSION: The SLN technique was favorably used in vaginal cancer in this series. It assists in identifying an inguinal and/or pelvic lymphatic drainage. When performed accurately (technetium Tc 99m nanocolloid, lymphoscintigraphy and/or SPECT/CT, blue dye), this technique predicts regional nodal status. This allows tumor stage-adjusted therapy. Single photon emission computed tomography/CT improves preoperative planning and facilitates detection, thus enhancing the clinical value of the SLN technique and improving the oncologic safety of surgery.

Cervical screening test results associated with 265 histopathologic diagnoses of cervical glandular neoplasia.

OBJECTIVES: To document screening test histories of women with histopathologic cervical glandular neoplasia (CGN) in a large integrated health system using new methods of cervical screening. METHODS: Cervical screening test results were reviewed for 265 patients with histopathologic diagnoses of CGN, including 168 adenocarcinoma in situ, 80 invasive cervical adenocarcinoma, and 17 invasive cervical adenosquamous carcinoma cases. RESULTS: Among 222 cases with known triggers of diagnostic studies, 211 (95%) had recent abnormal Papanicolaou (Pap) test results. Glandular cell abnormalities were the most common recent abnormal Pap test finding in 130 (61.6%) of 211; squamous cell abnormalities alone were documented in 81 (38.4%) of 211, reflecting coexisting cervical intraepithelial neoplasia (CIN) in 60% of CGN cases. Among 114 CGN cases with additional Pap tests more than 4 months to 3 years before CGN diagnosis, 70 (61.4%) had only earlier negative Pap test results. Among 72 CGN cases with recent human papillomavirus (HPV) test results, 70 (97.2%) tested HPV positive. Among 29 CGN cases with HPV test results more than 4 months to 3 years before CGN diagnosis, 25 (86.2%) tested HPV positive. CONCLUSIONS: Conservative cytologic screening practices and HPV cotesting can facilitate early diagnoses of CGN.

Comparison of the prognostic value of the 6th and 7th editions of the Union for International Cancer Control TNM staging system in patients with lower esophageal cancer undergoing neoadjuvant chemotherapy followed by surgery.

Carcinoma of the esophagus is classified according to the Union for International Cancer Control (UICC) TNM staging system. The 7th edition of the UICC TNM staging system was published in 2009. This is the first study to compare the prognostic value of the TNM 6th and 7th editions in patients with esophageal carcinoma treated with chemotherapy followed by surgery. Two hundred forty-three patients with esophageal carcinoma were retrospectively selected from two referral centers. All patients received chemotherapy before surgery. Histopathologic data from the resection specimens were retrieved and restaged according to the TNM 7th edition. Disease-specific survival curves were plotted for depth of tumor invasion (ypT), lymph node status (ypN), and ypTNM stage and then compared. Median follow-up after surgery was 2.5 years (range 0.2-9 years). Survival analysis using the log-rank method revealed that there was a significant difference in survival between ypT4 disease and ypT3 disease (P= 0.003), but no difference between ypT0, ypT1, ypT2, and ypT3 categories irrespective of TNM edition used. Survival probability was significantly different between ypN0 and ypN1 (P= 0.001 for TNM 6th and 7th edition), as well as ypN2 and ypN3 (TNM 7th edition, P= 0.004), but not between ypN1 and ypN2 (TNM 7th edition, P= 0.89). Neither the TNM 6th nor 7th edition T staging provides accurate survival probability stratification. However, the advantage of the 7th edition is the introduction of a third tier in survival stratification for patients with nodal involvement.

Successful treatment with GEMOX in patient with metastatic pancreatic adenosquamous carcinoma.

BACKGROUND: Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of pancreatic cancer characterized by a dual histological component and aggressive behavior. This form is not well known, its histogenesis is uncertain, and there are different opinions on the diagnostic histopathological criteria. The differential diagnosis with more common ductal adenocarcinoma, squamous cell carcinoma, squamous or adenosquamous metastases is complex. The available therapies do not improve the poor prognosis and it is difficult to find long-term survivors (more than 1 year), even after demolitive surgery with complementary therapies. CASE REPORT: We report a case of advanced PASC with excellent progression-free survival and overall survival, 20 months and 29 months, respectively. Furthermore, an almost complete response was obtained to first-line chemotherapy with gemcitabine/oxaliplatin (GEMOX) followed by maintenance gemcitabine. CONCLUSION: GEMOX followed by gemcitabine as maintenance could be an effective treatment for this pancreatic entity. Further reports are needed to confirm this outcome.

Neoadjuvant and adjuvant chemotherapy of cervical cancer: mature results of the phase 2 PBM-PFU protocol.

OBJECTIVE: The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonrandomized, phase 2 Yale University cisplatin, bleomycin, methotrexate, and 5-FU protocol are presented. METHODS: Sixty-seven patients were prospectively accrued with a median follow-up of 5.4 years, and standard parameters of toxicity and efficacy were studied. Both univariate and multivariate analyses were applied. RESULTS: The 5-year disease-free survival of 78% for the 25 patients in the adjuvant group, of which 80% had high-risk features including positive margins, parametria, and lymph nodes and 28% had adenocarcinomas, was comparable to recent relevant literature. Only 64% of patients in this group received consolidation radiation therapy, which did not impact on survival. Only 12% of patients recurred distantly. Notably, those who received 4 months or more of chemotherapy had prolonged survival (P = 0.012). In the neoadjuvant group, chemotherapy response rate among 42 patients (with stages 1B-IIIB cancer) was 79% (50% partial response, 29% complete response), and no patient progressed. In the subgroup of 22 patients who underwent surgery after chemotherapy, 59% had nonsquamous histology. Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy. Ninety-five percent received postoperative radiation therapy. There was a 9% pathologic complete response rate, with positive lymph nodes found in 27%. Notably, those who received 3 months or less of chemotherapy had improved overall survival (P = 0.030). Survival rates of these 22 patients at 3 and 5 years were 73% and 63%, respectively. Although not randomized, these survival rates were similar to those achieved with chemoradiation. CONCLUSIONS: Although there are several logistical/design features of the cisplatin, bleomycin, methotrexate, and 5-FU regimen that are not in line with the current chemotherapy era, our experience with this well-tolerated regimen can serve as a proof of principle. Our data suggests that both neoadjuvant and adjuvant cisplatin-based neoadjuvant chemotherapy may have their place. It also raises the possibility that the optimal duration of chemotherapy in adjuvant cases should be longer than in neoadjuvant cases.