Preoperative Japanese Society for the Surgery of the Foot Lesser toe score and erythrocyte sedimentation rate influence wound healing following rheumatoid forefoot surgery.

OBJECTIVES: Delayed wound healing is one of the most common complications following forefoot surgery in patients with rheumatoid arthritis. We aimed to identify the risk factors for delayed wound healing following rheumatoid forefoot surgery. METHODS: Consecutive patients who underwent primary rheumatoid forefoot surgery (86 feet; 53 patients) between April 2008 and February 2019 were retrospectively evaluated. Clinical data, including smoking history, duration of the disease, presence of diabetes mellitus, medication, white blood cell count, erythrocyte sedimentation rate (ESR), C-reactive protein, the surgical procedure performed, and the Japanese Society for Surgery of the Foot (JSSF) scores, were collected. RESULTS: Delayed wound healing was identified in 20 of 86 (23.3%) feet. In univariate analysis, participants showing delayed healing were older at the time of surgery (p = .04), their ESR was higher (p = .0006), and their total (p = .019) and pain (p = .016) scores on the JSSF Lesser toe scale were lower than those showing normal healing. In multivariable analysis, both the total preoperative JSSF Lesser toe scale score (p = .0239) and ESR (p = .0126) remained significant risk factors for delayed wound healing. CONCLUSIONS: After rheumatoid forefoot surgery, surgeons should pay more attention to wound care in patients with lower preoperative JSSF Lesser toe score and high ESR.

Usefulness of positron emission tomography (PET)/contrast-enhanced computed tomography (CE-CT) in discriminating between malignant and benign intraductal papillary mucinous neoplasms (IPMNs).

BACKGROUND/OBJECTIVES: We evaluated the usefulness of positron emission tomography (PET)/contrast-enhanced computed tomography (CE-CT) in discriminating between malignant and benign intraductal papillary mucinous neoplasms (IPMNs). METHODS: PET/CE-CT imaging was conducted on 29 IPMN lesions, which subsequently underwent surgery. Preoperative findings on PET/CE-CT imaging were compared with the histological findings of the resected specimens to determine the diagnostic accuracy of PET/CE-CT imaging for evaluation of the differential diagnosis between benign and malignant IPMNs. RESULTS: The final diagnoses of the 29 IPMN lesions were 9 benign and 20 malignant. Overall, 18 of the 20 malignant cases were positive for FDG uptake, while 7 of 9 benign cases were negative. The sensitivity, specificity, and diagnostic accuracy for benign/malignant differentiation using FDG uptake as a marker were 90.0%, 77.8%, and 86.2%, respectively. When guideline-based high-risk findings were used as markers, sensitivity, specificity, and diagnostic accuracy for mural nodules were 50.0%, 66.7%, and 55.2%, while they were 40.0%, 56%, and 48.3% for main duct dilatation, respectively. CONCLUSIONS: FDG uptake on PET is a useful new marker for malignancy in benign/malignant differentiation. Because PET/CE-CT imaging is a noninvasive imaging modality that can evaluate FDG uptake in addition to the conventional high-risk findings, we believe it should be the first-line method for determining therapeutic approaches to IPMN.

The Japanese Guidelines for Breast Cancer Screening.

OBJECTIVE: The incidence of breast cancer has progressively increased, making it the leading cause of cancer deaths in Japan. Breast cancer accounts for 20.4% of all new cancers with a reported age-standardized rate of 63.6 per 100 000 women. METHODS: The Japanese guidelines for breast cancer screening were developed based on a previously established method. The efficacies of mammography with and without clinical breast examination, clinical breast examination and ultrasonography with and without mammography were evaluated. Based on the balance of the benefits and harms, recommendations for population-based and opportunistic screenings were formulated. RESULTS: Five randomized controlled trials of mammographic screening without clinical breast examination were identified for mortality reduction from breast cancer. The overall relative risk for women aged 40-74 years was 0.75 (95% CI: 0.67-0.83). Three randomized controlled trials of mammographic screening with clinical breast examination served as eligible evidence for mortality reduction from breast cancer. The overall relative risk for women aged 40-64 years was 0.87 (95% confidence interval: 0.77-0.98). The major harms of mammographic screening were radiation exposure, false-positive cases and overdiagnosis. Although two case-control studies evaluating mortality reduction from breast cancer were found for clinical breast examination, there was no study assessing the effectiveness of ultrasonography for breast cancer screening. CONCLUSIONS: Mammographic screening without clinical breast examination for women aged 40-74 years and with clinical breast examination for women aged 40-64 years is recommended for population-based and opportunistic screenings. Clinical breast examination and ultrasonography are not recommended for population-based screening because of insufficient evidence regarding their effectiveness.

A meta-analysis of mammographic screening with and without clinical breast examination.

Mammographic screening with clinical breast examination has been recommended in Japan since 2000. Although mammographic screening without clinical breast examination has not been recommended, its introduction is anticipated. The efficacies of mammographic screening with and without clinical breast examination were evaluated based on the results of randomized controlled trials. PubMed and other databases for studies published between 1985 and 2014 were searched. The study design was limited to randomized controlled trials to evaluate mortality reduction from breast cancer. Five studies were eligible for meta-analysis of mammographic screening without clinical breast examination. The relative risk for women aged 40-74 years was 0.75 (95% confidence interval, 0.67-0.83). Three studies evaluated the efficacy of mammographic screening with clinical breast examination. The relative risk for women aged 40-64 years was 0.87 (95% confidence interval, 0.77-0.98). The number needed to invite was always lower in mammographic screening without clinical breast examination than in mammographic screening with clinical breast examination. In both screening methods, the number needed to invite was higher in women aged 40-49 years than in women aged 50-70 years. These results suggest that mammographic screening without clinical breast examination can afford higher benefits to women aged 50 years and over. Although evidence of the efficacy of mammographic screening without clinical breast examination was confirmed based on the results of the randomized controlled trials, a Japanese study is needed to resolve local problems.

Incidence of metachronous gastric cancer in the remnant stomach after synchronous multiple cancer surgery.

BACKGROUND: In the preoperative evaluation for gastric cancer, high-resolution endoscopic technologies allow us to detect small accessory lesions. However, it is not known if the gastric remnant after partial gastrectomy for synchronous multiple gastric cancers has a greater risk for metachronous cancer. The purpose of this study was to determine the incidence of metachronous cancer in this patient subset compared with that after solitary cancer surgery. METHODS: Data on a consecutive series of 1,281 patients gastrectomized for early gastric cancer from 1991 to 2007 were analyzed retrospectively. The 715 gastric remnants after distal gastrectomy were periodically surveyed by endoscopic examination in Shikoku Cancer Center. Among those surveyed cases, 642 patients were pathologically diagnosed with solitary lesion (SO group) and 73 patients with synchronous multiple lesions (MU group) at the time of the initial surgery. RESULTS: In the follow-up period, 15 patients in the SO group and 3 patients in the MU group were diagnosed as having metachronous cancer in the gastric remnant. The cumulative 4-year incidence rate was 1.9 % in the SO group and 5.5 % in the MU group. The difference did not reach the significant level by the log-rank test. CONCLUSIONS: The incidence of metachronous cancer is higher after multiple cancer surgery; however, the difference is not statistically significant.

Hand-sewn anastomotic technique after esophageal cancer resection.

BACKGROUND/AIMS: Mechanical stapled anastomosis can be performed easily and quickly in esophagogastrostomy after esophageal cancer resection. However, we have performed cervical hand-sewn anastomosis in the esophagogastrostomy. Here we introduce the surgical technique and report the outcomes after the anastomosis. METHODOLOGY: The gastric tube is pulled up via the posterior mediastinal route. A single layer of Gambee sutures is used to approximate the cervical esophagus and the posterior wall of the gastric tube in end-to-side fashion. After the anastomosis, the redundant part in the gastric tube apex is removed. We analyzed 152 consecutive patients who underwent this anastomosis in our institute from 1999 to 2012. RESULTS: There was no postoperative mortality. We experienced anastomotic leakage in 7 patients (5%) and anastomotic stenosis in 5 patients (3%). CONCLUSIONS: The anastomotic complication rates in the hand-sewn anastomosis were comparable to those of the mechanical stapled anastomosis in the previous reports.

A case of EBV-associated inflammatory pseudotumor of the spleen.

Inflammatory pseudotumors (IPTs) of the spleen are rare and have often been reported to be associated with Epstein-Barr virus (EBV). Radiographically differentiating IPTs of the spleen from other malignant tumors is challenging, and splenectomy is often performed as a definitive treatment. We report a case of an EBV-associated splenic IPT in a male patient in his 70s. Contrast-enhanced computed tomography (CT) revealed a splenic mass that increased from 2.4 cm to 3.9 cm in diameter over one year. Magnetic resonance imaging (MRI) revealed that the mass showed a slightly high intensity on T1-weighted images and heterogeneous low intensity on T2-weighted images. On dynamic contrast-enhanced MRI, the mass showed weak and gradual inhomogeneous enhancement. A 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT demonstrated increased FDG uptake in the mass. Splenectomy was performed and the pathological diagnosis was EBV-associated IPT. EBV-associated splenic IPT can mimic malignant tumors on imaging, making it challenging to differentiate them from other splenic diseases.

Impact of diradical character on two-photon absorption: bis(acridine) dimers synthesized from an allenic precursor.

The two-photon absorption (TPA) of a bis(acridine) dimer (8) having singlet diradical character in its ground state was found to be enhanced by more than 2 orders of magnitude as compared to its closed-shell counterpart (12), which has the same structural backbone and atom composition. The dimer, a tetracation species consisting of two connected acridinium cation moieties with high coplanarity, was obtained during our attempts to synthesize triplet carbenes by double oxidation of an allenic precursor (3b). High conjugation over the two aromatic rings connected by dimerization was revealed by X-ray analysis, and a small HOMO-LUMO gap was found in the visible-near-infrared one-photon absorption spectrum in solution and in the crystalline state, exhibiting that the ground state of 8 has singlet diradical nature. Ab initio molecular orbital calculations of the ground state also suggested that 8 has an intermediate diradical character (y) of 0.685. Interconversion between diradical tetracation dimer 8 and closed-shell dication dimer 12 was achieved by oxidation/reduction in good yields and was accompanied by formation of monoradical trication dimer 13 as an intermediate. TPA measurements at near-infrared wavelengths revealed that diradical dimer 8 has large TPA cross sections (3600 GM at 1200 nm), while closed-shell 12 has TPA cross sections of <21 GM. This result represents a straightforward comparison between the TPA activity of molecules with the same structural backbone and atom composition but with different degree of the diradical character, supporting the theoretical prediction that enhanced TPA intensity can be observed in the intermediate y region (0 < y < 1).

Syntheses and properties of graphyne fragments: trigonally expanded dehydrobenzo[12]annulenes.

We present herein the synthesis and properties of the largest hitherto unknown graphyne fragment, namely trigonally expanded tetrakis(dehydrobenzo[12]annulene)s (tetrakis-DBAs). Intramolecular three-fold alkyne metathesis reactions of hexakis(arylethynyl)DBAs 9 a and 9 b using Fürstner's Mo catalyst furnished tetrakis-DBAs 8 a and 8 b substituted with tert-butyl or branched alkyl ester groups in moderate and fair yields, respectively, demonstrating that the metathesis reaction of this protocol is a powerful tool for the construction of graphyne fragment backbones. For comparison, hexakis(arylethynyl)DBAs 9 c-g have also been prepared. The one-photon absorption spectrum of tetrakis-DBA 8 a bearing tert-butyl groups revealed a remarkable bathochromic shift of the absorption cut-off (λcutoff ) compared with those of previously reported graphyne fragments due to extended π-conjugation. Moreover, in the two-photon absorption spectrum, 8 a showed a large cross-section for a pure hydrocarbon because of the planar para-phenylene-ethynylene conjugation pathways. Hexakis(arylethynyl)-DBAs 9 c-e and 9 g and tetrakis-DBA 8 b bearing electron-withdrawing groups aggregated in chloroform solutions. Comparison between the free energies of 9 e and 8 b bearing the same substituents revealed the more favorable association of the latter due to stronger π-π interactions between the extended π-cores. Polarized optical microscopy observations, DSC, and XRD measurements showed that 8 b and 9 e with branched alkyl ester groups displayed columnar rectangular mesophases. By the time-resolved microwave conductivity method, the columnar rectangular phase of 8 b was shown to exhibit a moderate charge-carrier mobility of 0.12 cm(2) V(-1) s(-1) . These results indicate that large graphyne fragments can serve as good organic semiconductors.

Long-term outcome after proximal gastrectomy with jejunal interposition for gastric cancer compared with total gastrectomy.

BACKGROUND: Proximal gastrectomy (PG) has been widely accepted as treatment for early gastric cancer located in the upper third of the stomach. Reconstruction by jejunal interposition has been known to reduce reflux esophagitis for PG patients. The aim of this study was to compare the long-term outcomes of patients who underwent PG with jejunal interposition with those treated by total gastrectomy (TG). METHODS: Data on 102 cases of PG with jejunal interposition and 49 cases of TG with Roux-Y reconstruction for gastric cancer were analyzed retrospectively in terms of overall survival, weight maintenance, anemia and nutritional status, and endoscopic findings. RESULTS: Median follow-up time was 59 months in the both groups. There was no significant difference in the overall 5-year survival rate between the PG group (94%) and the TG group (84%). The PG group showed significantly better body weight maintenance at the first year. The laboratory blood tests showed that the PG group had a significantly better red blood cell count and hemoglobin and hematocrit levels at the second and third year. However, postoperative endoscopic surveillance detected reflux esophagitis (3%), peptic ulcer (9%), and metachronous gastric cancer (5%) in the PG group. CONCLUSIONS: Proximal gastrectomy maintains comparable oncological radicality to TG and is preferred over TG in terms of preventing postoperative anemia. However, periodic endoscopic follow-up is necessary to monitor the upper gastrointestinal tract.

[A case of reversible encephalopathy syndrome caused by hyponatremia during neoadjuvant 5-FU+CDDP therapy for esophageal cancer].

We present a case of reversible encephalopathy syndrome caused by hyponatremia during neoadjuvant chemotherapy with 5-FU+CDDP for esophageal cancer. A 52-year-old woman visited another hospital with the complaint of discomfort during swallowing. Upper gastrointestinal endoscopy revealed an ulcerated lesion in the lower thoracic esophagus, which was pathologically diagnosed as squamous cell carcinoma. She was admitted to our institution, and the diagnosis of esophageal cancer Mt-Lt, type 2, cT2N1M0, stage II was made. We obtained informed consent for her treatment with both CRT and surgery, and she selected surgery. Therefore, she was administered neoadjuvant chemotherapy with 5-FU+CDDP therapy. On day 4, abnormalities of the central nerve, such as unconsciousness, difficulty in speaking, and muscle cramps were, observed. After the examinations she was diagnosed with encephalopathy. It should be noted that hyponatremia induced by renal sodium wasting syndrome(RSWS)was considerd to be the cause, and we report our case with the literature cited.

Desmoid tumor occurrence following gastric cancer surgery: A report of two cases.

INTRODUCTION AND IMPORTANCE: While rare, desmoid tumors can develop after abdominal surgery and are difficult to differentiate from recurrent tumors following cancer resection. In this report, we describe two cases of desmoid tumors that occurred following gastric cancer procedures and were successfully treated with surgical resection. CASE PRESENTATION: In Case 1, a 77-year-old woman underwent open distal gastrectomy for gastric cancer followed by Roux-en-Y reconstruction. The pathological diagnosis was stage IIB T3N1M0 disease. Four years postsurgically, computed tomography (CT) revealed a 2.4 cm tumor lesion in the upper abdomen. Desmoid tumor was the most suspected tumor, for which a resection with partial resection of the jejunum was performed. In case 2, a 60-year-old man underwent open distal gastrectomy for gastric cancer and Billroth I reconstruction; the pathological diagnosis was T1aN0M0 stage IA. Two years later, CT revealed a 4.0 cm tumor lesion in the upper abdomen. As in Case 1, desmoid tumor was most suspected, a tumor resection with partial resection of the jejunum was performed. Based on the pathological findings, the tumors were diagnosed as desmoid tumor. There had been no recurrence of either gastric cancer or the desmoid tumor in both cases. CLINICAL DISCUSSION: Although active surveillance has been recommended for desmoid tumors recently, surgical resection is appropriate when recurrence cannot be ruled out. CONCLUSIONS: Desmoid tumors should be included in the differential diagnosis when intra-abdominal tumors occur after surgery for gastric cancer. Complete resection with adequate margins can prevent desmoid recurrence.

Surgical resection of a retroperitoneal liposarcoma producing insulin-like growth factor II: a case report.

BACKGROUND: Tumor-produced high molecular weight insulin-like growth factor-II (big insulin-like growth factor-II) is considered to cause non-islet cell tumor hypoglycemia. This paper presents a case of surgically resected retroperitoneal liposarcoma that produced big insulin-like growth factor-II. CASE PRESENTATION: Here, we report the case of a 62-year-old woman who presented with an abdominal mass and hypoglycemia. Non-islet cell tumor hypoglycemia due to retroperitoneal liposarcoma was suspected. After complete resection of the tumor, the patient's hypoglycemia improved and big insulin-like growth factor-II disappeared in the molecular weight analysis of serum insulin-like growth factor-II by western blotting. The patient had no tumor recurrence or reappearance of hypoglycemia 16 months after the operation without any adjuvant therapy. CONCLUSIONS: Although insulin-like growth factor-II-producing tumors are generally large and difficult to operate on, surgical resection is currently the most effective and only treatment; thus, it is essential to attempt resection aggressively.

Enhancement of second hyperpolarizabilities in open-shell singlet slipped-stack dimers composed of square planar nickel complexes involving o-semiquinonato type ligands.

Using the spin-unrestricted hybrid density functional theory method, we have investigated the intermolecular interaction effects on the longitudinal static second hyperpolarizability (γ) of open-shell singlet slipped-stack dimers composed of singlet diradical square planar nickel complexes involving o-semiquinonato type ligands, Ni(o-C(6)H(4)X(2))(2) (where X = O, NH, S, Se, PH). For comparison, we have also examined the γ values of a closed-shell singlet slipped-stack dimer composed of closed-shell monomers Ni[o-C(6)H(4)S(NH(2))](2). It is found that for interplanar distance ranging between 3.0 and 5.0 Šthe slipped-stack dimers with intermediate monomer diradical characters exhibit larger γ values per monomer (γ(dimer)/2) than those with large monomer diradical characters or than the closed-shell dimer. These results extend the domain of validity of the relationship found between γ and the diradical character for individual molecules. It also turns out that the ratio R = (γ(dimer)/2)/γ(monomer) increases upon decreasing the interplanar distance and that this increase is larger for intermediate diradical character than for the other cases. These phenomena have been analyzed by considering the γ density distributions of the dimers, demonstrating a significant field-induced third-order charge transfer between the monomers in the case of intermediate diradical character. The present results indicate that open-shell singlet slipped-stack aggregates composed of monomers with intermediate diradical characters constitute another mean for achieving highly efficient and tunable third-order nonlinear optical materials.

Two-photon absorption properties of two-dimensional π-conjugated chromophores: combined experimental and theoretical study.

The two-photon absorption (TPA) properties of four TPEB [tetrakis(phenylethynyl)benzene] derivatives (TD, para, ortho, and meta) with different donor/acceptor substitution patterns have been investigated experimentally by the femtosecond open-aperture Z-scan method and theoretically by the time-dependent density-functional theory (TDDFT) method. The four compounds show relatively large TPA cross sections, and the all-donor substituted species (TD) displays the largest TPA cross-section σ(2) = 520 ± 30 GM. On the basis of the calculated electronic structure, TD shows no TPA band in the lower energy region of the spectrum because the transition density is concentrated on particular transitions due to the high symmetry of the molecular structure. The centrosymmetric donor-acceptor TPEB para shows excitations resulting from transitions centered on D-π-D and A-π-A moieties, as well as transition between the D-π-D and A-π-A moieties; this accounts for the broad nature of the TPA bands for this compound. Calculations for two noncentrosymmetric TPEBs (ortho and meta) reveal that the diminished TPA intensities of higher-energy bands result from destructive interference between the dipolar and three-state terms. The molecular orbitals (MOs) of the TPEBs are derivable with linear combinations of the MOs of the two crossing BPEB [bis(phenylethynyl)benzene] derivatives. Overall, the characteristics of the experimental spectra are well-described based on the theoretical analysis.

[A case of advanced gastric cancer with tumor embolus in the portal vein successfully treated with S-1 and CDDP therapy].

A 50-year-old man with advanced gastric cancer and a tumor embolus in the portal vein was referred to our hospital. We diagnosed the tumor as cStage III B (cT3, cN2, cH0, P0, M0) gastric cancer, and selected neoadjuvant S-1 (80 mg/m2) and CDDP (60 mg/m2) therapy for him. After 2 courses of chemotherapy, the embolus in the portal vein disappeared. After additional chemotherapy, the primary tumor and regional lymph node revealed a partial response (PR), and judging from the results from the barium meal study, upper GI endoscopic findings and CT scan, a total gastrectomy with lymph node dissection was performed.

[Type 4 advanced gastric cancer responding to histological complete response after neoadjuvant S-1 combined with CDDP therapy-report of a case].

A 75-year-old man with type 4 advanced gastric cancer was referred to our hospital. We diagnosed the tumor as cStage III B(cT4a, cN2, cM0)gastric cancer. We selected neoadjuvant S-1 combined with CDDP therapy for him. After 2 courses of chemotherapy, the extension of the gastric wall improved. After an additional 2 courses of chemotherapy, the primary tumor revealed a partial response(PR), judged from a barium meal study and upper GI endoscopic findings, and a total gastrectomy with lymph node dissection was performed. The pathological specimens showed no cancer cells in the gastric wall and lymph nodes, so the histological effect was judged as Grade 3.

Changes in Physical Function and Effects on QOL in Patients after Pancreatic Cancer Surgery.

This study examined the changes in physical function and quality of life (QOL) of postoperative patients with pancreatic cancer for 3 months after surgery and examined the factors affecting the QOL at the 3 months after surgery. METHODS: This study comprised 32 pancreatic cancer patients who underwent surgery at our hospital. Among these patients, 20 patients for whom data was measured before surgery to 3 months after surgery were selected for statistical analyses: 8 males and 12 females, 69.8 ± 7.4 years. The preoperative and postoperative rehabilitation was given to patients under the guidance of a physiotherapist. Nutritional status, body composition, physical function, gait assessments, and QOL were investigated. RESULTS: Body weight, body fat mass, body fat percentage, body mass index (BMI), and muscle mass significantly decreased 3 months after surgery compared with their respective preoperative values. The mean grip strength at the time of 3 months after the surgery had decreased significantly from 27.3 kg to 24.5 kg. The mean skeletal muscle mass index (SMI) had decreased significantly from 6.3 kg before surgery to 5.9 kg after the surgery. The QOL scores for global health status, physical, and role showed significant decreases 2 weeks after surgery compared with the respective preoperative scores. Significant improvements in these scores were observed 3 months after surgery compared with the respective scores 2 weeks after surgery. Physical function assessments after surgery were associated with QOL 3 months after surgery. CONCLUSION: Recovery of patients after pancreatic cancer surgery in body weight, BMI, body fat percentage, body fat percentage, muscle mass, SMI, and grip strength was not sufficient at the time of 3 months after surgery. It has been observed that physical function of patients has affected the improvement of QOL.

Giant electric field effect on the second hyperpolarizability of symmetric singlet diradical molecules.

This contribution reveals the effects of a static electric field on the static second hyperpolarizability γ of symmetric singlet diradical molecules using the valence configuration interaction scheme. It is found that under the effect of a field, the component of γ along the axis joining the two radical sites can be gigantically (approximately two to three orders) enhanced for symmetric diradicals having intermediate diradical characters with respect to those of closed-shell and pure diradical molecules in the absence of a field. Moreover, this electric field enhancement of γ increases as a function of the diradical character. These results and their analysis propose therefore a new strategy to design materials with exceptional nonlinear optical responses.

Long-range corrected density functional theory study on static second hyperpolarizabilities of singlet diradical systems.

Within the spin-unrestricted density functional theory (DFT) the long-range correction (LC) scheme combined with the Becke-Lee-Yang-Parr exchange-correlation functional, referred to as LC-UBLYP method, has been applied to the calculation of the second hyperpolarizability (gamma) of open-shell singlet diradical systems of increasing complexity and has demonstrated good performance: (i) for the simplest H(2) dissociation model, the gamma values calculated by the LC-UBLYP method significantly overshoot the full configuration interaction result but reproduce qualitatively the evolution of gamma as a function of the diradical character, (ii) for small singlet diradical 1,3-dipole systems, the diradical character dependence of gamma determined by the UCCSD and UCCSD(T) reference methods is reproduced semiquantitatively by the LC-UBLYP method except in the small diradical character region, where the spin-unrestricted solutions coincide with spin-restricted solutions, (iii) the LC-UBLYP method also closely reproduces the UCCSD(T) results on the diradical character dependence of gamma of the p-quinodimethane model system, particularly in the intermediate and large diradical character regions, whereas it shows an abrupt change for a diradical character (y) close to 0.2 originating from the triplet instability, (iv) the reliability of LC-UBLYP to reproduce reference coupled cluster results on open-shell singlet systems with intermediate and large diradical characters has also been substantiated in the case of gamma of 1,4-bis-(imidazol-2-ylidene)-cyclohexa-2,5-diene (BI2Y), then (v), for real systems built from a pair of phenalenyl radicals separated by a conjugated linker, the LC-UBLYP results have been found to closely match the UBHandHLYP values-which, for small systems are in good agreement with those obtained using correlated molecular orbital methods-whereas the UB3LYP results can be much different. These results are not only important from the viewpoint of an efficient determination of the nonlinear optical properties of open-shell singlet systems, but also from the viewpoint of defining new challenges for elaborating improved exchange-correlation functionals.